eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
6/2019
vol. 15
 
Share:
Share:
more
 
 
Basic research

Mechanism of microRNA-431-5p-EPB41L1 interaction in glioblastoma multiforme cells

Xiaoyong Han
,
Xirui Wang
,
Hui Li
,
Hui Zhang

Arch Med Sci 2019; 15 (6): 1555–1564
Online publish date: 2019/09/26
Article file
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
 

Introduction

Glioblastoma multiforme (GBM) is a kind of malignant brain tumor prevalent in adults, with the characteristics well adapted to poorly immunogenic and hypoxic conditions [1]. Effective treatment of GBM is impeded due to the high proliferation, migration and invasion of GBM cells [2]. GBM cells migrate by degrading the extracellular matrix, so it is difficult to have GBM cells eradicated completely by surgery [3]. According to the existing research, the median survival time of patients suffering from GBM is no more than 15 months, and 5-year survival prognosis of the patients is less than 10%, even if treated with aggressive therapy strategies [4, 5]. The exact molecular mechanisms of GBM cell proliferation are still unclear, so further studies on the molecular mechanisms are urgently needed for the development of effective therapeutic strategies.

MicroRNAs (miRNAs) are non-coding RNA molecules comprising 20 to 25 nucleotides [6]. MiRNAs regulate gene expression, which is associated with physiological and pathological processes [7]. Particularly, they are involved in tumorigenesis [8]. MiRNAs have been proved to have a critical relationship with various kinds of human cancers, such as lung and hepatic cancers [9, 10]. They can act as tumor suppressors by targeting oncogenes. Enhanced evidence has accumulated revealing that several miRNAs are involved in the biological processes associated with GBM progression, including cell proliferation, migration, invasion, apoptosis, etc. For example, miR-522 has been reported to be positively correlated with GBM cell proliferation by down-regulating the expression of PHLPP1 [11]. MiR-1908 has been proved to function as a GBM oncogene by suppressing the PTEN tumor suppressor pathway [12]. The investigation of miRNAs would be of great importance and the exploration of the potential miRNAs may help us identify biomarkers, as well as explore novel therapies for patients with GBM. Initially, miR-431 dysregulation was specific to the nervous system, such as spinal muscular atrophy [13]. Additionally, the down-regulation of miR-431 inhibits the viability of GBM cells by regulating SOCS6 [14]. Recent evidence has shown its relationship with development of other tumors. For instance, miR-431 was detected to have elevated expression in colorectal cancer [15], and its overexpression in hepatocellular carcinoma cells was confirmed to inhibit cell invasion and migration [16].

The dysregulation of miR-431 could affect tumorigenesis by regulating its target mRNAs. In this study, we focused on targeting the relationship between miR-431-5p and EPB41L1 in GBM cells. EPB41 encodes a multifunctional protein that mediated the communication between the erythrocyte cytoskeleton and the overlying plasma membrane. EPB41 binds to and stabilizes dopamine receptors at the neuronal plasma membrane. EPB41L1 was reported to act as a potential tumor suppressor [17]. But there is no evidence clarifying the correlation between miR-431 and EPB41L1. Mechanically, we have found that miR-431-5p enhances the proliferation and invasion of GBM cells by suppressing the expression of EPB41L1.

Material and methods

Tissue samples

Glioblastoma multiforme tissues and the adjacent tissues (located at least 2 cm from the tumor edges) were obtained from 30 patients who received surgical treatment in Cangzhou Central Hospital, Cangzhou, Hebei, China from January, 2015 to March 2016. Samples were immediately frozen in liquid nitrogen until analysis [18, 19].

Cell culture

The normal brain glial cell line HEB and GBM cell lines U251, A172, U-118 and U87 (purchased from Chinese Academy of Sciences, Shanghai, China) were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) [1922] with 10% fetal bovine serum (FBS) at 37°C under the atmosphere of 5% CO2 and 95% air.

Cell transfection

U87 cells were respectively transfected with miR-431-5p mimics (miR-mimics), miR-431-5p inhibitor (anti-miR), miR-431-5p inhibitor negative control (anti-NC), and miR-431-5p mimics negative control (miR-NC) using Lipofectamine 2000 reagent (GenePharma Co., Ltd., Shanghai, China). The lentiviral vector (plenti-GIII-UbC) was used to construct a recombinant vector (plenti-GIII-Ubc-EPB41L1) which was then transfected into U87 cells (plenti-EPB41L1). Meanwhile, U87 cells transfected with pLenti-GIII-UbC-Null (plenti-Null) were the negative control group.

RNA extraction and qRT-PCR

Frozen tissues and cell samples were defrosted, and then TRIzol reagent (Invitrogen, Carlsbad, CA) was added to extract total RNA according to the instructions. QuantiTect SYBR Green RT-PCR kit (Qiagen, Hilden, Germany) was applied to evaluate the relative expression of miR-431-5p and EPB41L1 to U6 or GAPDH (the normalizer), respectively. The expression level was also calculated using the 2–ΔΔCt method. The primer sequences (synthesized by Ribo Bio, Guangzhou, China) are given in Table I.

Table I

Primer sequences for qRT-PCR

cDNAForward primersReverse primers
MiR-431-5p5′-ACAGAACGUCCGGCAGUACGU-3′
U65′-CTCGCTTCGGCAGCACA-3′5′-AACGCTTCACGAATTTGCGT-3′
EPB41L15′-GGAGACAUUCUCUAGGAC-3′5′-UAAUUUACUAUGUUUCUG-3′
GAPDH5′-CCACCCAGAAGACTGTGGAT-3′5′-TTCAGCTCAGGGATGACCTT-3′

Western blot

Concentrations of the protein extracted from cells and tissues were measured using a bicinchoninic acid (BCA) protein assay kit (Beyotime Biotech, Haimen, China). A total of 30 μg of protein was resolved by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to immunoblot polyvinylidene difluoride membranes (Chemicon International, Millipore, Billerica, MA, USA). The membranes were blocked with 5% skimmed milk in Tris-buffered saline with 0.1% Tween (TBS-T) for 1 h, washed three times with TBS-T, and incubated for 10 h at 4°C with primary antibodies against EPB41L1 (1 : 2000) and GAPDH (1 : 2000) (Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA). The blots were then incubated with horseradish peroxidase-labeled secondary goat anti-rabbit (1 : 2000) or rabbit anti-goat antibodies (1 : 2000) (Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA). Membranes were visualized with enhanced chemiluminescence (ECL kit; Applygen Inst. Biotech, Beijing, China).

Dual luciferase reporter gene assay

The wild type or mutated 3′-UTR (replacing GCAAGAC by CGUUCG according to the prediction of TargetScan software) of EPB4L1 was inserted into the pMIR-REPORT luciferase vector (Promega, Madison, USA) to construct the pMIR-REPORT-wt or pMIR-REPORT-mut vector. The wild-type or mutated plasmid was co-transfected into U87 cells with miR-mimics or miR-NC. The empty pmirGLO vector (pGLO-NULL) was also transfected as a control. Cells were collected 48 h after transfection, and then the Dual Luciferase Reporter Assay System (Promega, Madison, USA) was used to detect the relative luciferase activity according to the protocol.

MTT assay

Fresh nutrient media were added to U87 cells after centrifugation. Then the cells (1 × 104/well) were transferred into 96-well plates. Samples were treated with MTT solution (6 mg/ml) strictly following the protocols for 4 h. After dissolving the crystals with 100 μl of DMSO, the optical density (OD) value was measured at 490 nm.

Flow cytometry analysis

Cells were fixed with 90% ethanol and then incubated with 50 mg/l RNase. Nuclei of cells were stained with 50 mg/l propidium iodide (PI) for 30 min. The cell cycle was examined using a flow-cytometer (CapitalBio, Beijing, China). Cell apoptosis was detected using the flow cytometer after incubating with Annexin V-FITC/PI reagent for 15 min.

Transwell assay

The Transwell invasion assay was performed using Matrigel invasion chambers (Corning Inc., USA). 1 × 105 cells in 15 μl medium were seeded in the upper chambers, and DMEM supplemented with 10% FBS was added to the bottom chamber to stimulate cell invasion. After 24 h of incubation, the bottom cells were fixed with 70% ethanol for 15 min, washed with PBS and stained with crystal violet. Six random fields of every well were photographed. The cell number of every view was counted under a microscope. The OD value of every well at 570 nm was measured as well.

Wound healing assay

Cells (2.5 × 105/ml) were seeded in 6-well plates and a 100 μl pipette tip was used to manually make a scratch 24 h after transfection on the surface of cell culture of each well. The scratch widths were initially measured (0 h) and re-measured after 24 h. The percentage of the shortened scratch width was defined as the wound healing rate (setting the wound healing rate as 0% initially).

Ethics approval

All patients signed informed content and the research was approved by the Hospital Ethical Committee. Consent for publication was obtained from all patients.

Statistical analysis

Differences between the groups were tested by Student’s t test or one-way ANOVA, using the SPSS 21.0 program (SPSS Inc., Chicago, IL, USA). p-values < 0.05, < 0.01, < 0.001 were considered statistically significant. All experiments were conducted in triplicate.

Results

MiR-431-5p expression in GBM tissues and cell lines

The expression of miR-431-5p was detected by qRT-PCR. We found that miR-431-5p was significantly overexpressed in GBM tissues compared to adjacent tissues (Figure 1 A, p < 0.01). MiR-431-5p was significantly overexpressed in GBM cell lines including U251, A172, U-118 and U87 compared to the normal brain glial cell line HEB (Figure 1 B, p < 0.01). The highest expression level of miR-431-5p was seen in the U87 cell line, which was selected for the following assays.

Figure 1

MiR-431-5p and EPB41L1 expression levels in GBM cells and tissues. A – Expression levels of miR-431-5p in GBM and adjacent tissues detected by qRT-PCR. B – miR-431-5p expression in different GBM cell lines and normal brain cell line HEB. C – mRNA levels of EPB41L1 in GBM and adjacent tissues detected by qRT-PCR. DEPB41L1 protein levels in GBM and adjacent tissues detected by Western blot

GBM – glioblastoma multiforme; **p < 0.01 was considered statistically significant.

/f/fulltexts/AOMS/37835/AMS-15-37835-g001_min.jpg

EPB41L1 was under-expressed in GBM tissues

Results of qRT-PCR showed that EPB1L1 mRNA expression was dramatically lower in GBM tissues than in adjacent tissues (Figure 1 C, p < 0.01). Similarly, the protein level of EPB1L1 detected by Western blot was also lower in GBM tissues compared with that in adjacent normal tissues (Figure 1 D).

MiR-431-5p directly targeted EPB41L1

The predicted gene sequences of wild-type and mutated miR-431-5p binding sites of EPB41L1 3′UTR are illustrated in Figure 2 A. PGLO-wt and pGLO-mut were constructed carrying wild-type or mutated EPB41L1 3′UTR. The results of dual luciferase reporter gene assay indicated that with the overexpression of miR-431-5p, the relative luciferase activity in the pGLO-wt group dramatically decreased compared with that in the miR-NC group (Figure 2 B, p < 0.01), while the pGLO-mut group showed no significant difference between pGLO-wt and miR-NC groups. The results of Western blot showed that the inhibition of miR-431-5p upregulated the expression of EPB41L1 in U87 cells (Figure 2 C). In conclusion, miR-431-5p could directly target EPB41L1 and inhibit its expression in GBM cells.

Figure 2

MiR-431-5p directly targeted EPB41L1 and inhibited its expression. A – Gene sequences of wild-type and mutated miR-431-5p binding sites of EPB41L1 3′UTR predicted by TargetScan. B – Luciferase activity of each group detected by dual luciferase reporter gene system. CEPB41L1 expression in transfected U87 cells detected by Western blot

**p < 0.01 was considered statistically significant.

/f/fulltexts/AOMS/37835/AMS-15-37835-g002_min.jpg

Influence of miR-431-5p and EPB41L1 expression on proliferation of GBM cells

Expression of miR-431-5p and EPB41L1 in 4, 8 and 12 h

Figure 3 shows the of EPB41L1 expression 4, 8 and 12 h after transfection in different groups. It was found that EPB41L1 expression significantly increased in the anti-miR group and the plenti-EPB41L1 group throughout the 12 h after transfection. However, the restoration experiments showed that within 4 h after the transfection, the inhibitory effect of miR-mimics on the expression of EPB41L1 was the strongest. After 4 h of transfection, the inhibitory effect of miR-mimics on the expression of EPB41L1 decreased but remained steady.

Figure 3

Expression of miR-431-5p and EPB41L1 in 4, 8 and 12 h after transfection in different groups. It was shown that EPB41L1 expression significantly increased in the anti-miR group and the plenti-EPB41L1 group throughout the 12 h after transfection. Within 4 h after transfection, the inhibitory effect of miR-mimics on the expression of EPB41L1 was the strongest. After 4 h transfection, the inhibition of miR mimics on the expression of EPB41L1 decreased but remained steady

/f/fulltexts/AOMS/37835/AMS-15-37835-g003_min.jpg

Proliferation of GBM cells detected by MTT assay

As shown in MTT assay results (Figure 4), the growth rate of U87 cells after transfection of miR-431-5p inhibitors significantly decreased compared with that in the control group (p < 0.01). Meanwhile, U87 cells transfected with plenti-EPB41L1 had a lower growth rate than those in the plenti-NULL group (p < 0.01), while U87 cells transfected with anti-NC or plenti-NULL, and cells co-transfected with plenti-EPB41L1 and miR-mimics showed no significant difference compared with the control group. The above results indicated that down-regulated expression of miR-431-5p and over-expressed EPB41L1 both inhibited the proliferation of GBM cells.

Figure 4

Influence of miR-431-5p and EPB41L1 expression on proliferation of GBM cells. Proliferation of U87 cells in different groups detected by MTT assay

GBM – glioblastoma multiforme; *p < 0.05 compared with anti-NC group corresponding timing point, #p < 0.05 compared with plenti- NULL group corresponding timing point.

/f/fulltexts/AOMS/37835/AMS-15-37835-g004_min.jpg

Influence of miR-431-5p and EPB41L1 expression on GBM cell cycle progression and apoptosis

Cell cycle progression detected by flow cytometry

As shown in Figure 5 A, both in the anti-miR group and the plenti-EPB41L1 group, the percentage of U87 cells in S phase was significantly lower than that in the control group (p < 0.01), while that of cells in G0/G1 phase was significantly higher (p < 0.05). However, the percentage of cells in each phase of anti-NC, plenti-NULL and plenti- EPB41L1 + miR-mimic groups did not show a statistically significant difference compared with the control group. Therefore, it was proved that decreasing miR-431-5p expression and increasing EPB41L1 expression both arrested cell growth in G0/G1 stage and inhibited cell proliferation, which could be hindered by miR-431-5p overexpression.

Figure 5

Influence of miR-431-5p and EPB41L1 expression on apoptosis of GBM cells. A – Cell cycle progression of U87 cells 48 h after transfection in different groups detected by flow cytometry; B – cell apoptosis of U87 cells in different groups 48 h after transfection detected by flow cytometry. Cell apoptosis rate in anti-miR and plenti-EPB41L1 groups was compared with the control group

GBM – glioblastoma multiforme; *p < 0.05 compared with anti-miR group, #p < 0.05 compared with plenti-NULL group.

/f/fulltexts/AOMS/37835/AMS-15-37835-g005_min.jpg

Cell apoptosis detected by flow cytometry

Cells in anti-miR and plenti-EPB41L1 groups showed a significantly higher apoptosis rate compared with those in the control group (Figure 5 B, p < 0.001), while there was no significant difference between the control group, anti-NC, plenti-NULL and plenti-EPB41L1 + miR-mimics groups. Therefore, it was demonstrated that decreasing miR-431-5p expression and increasing EPB41L1 expression both promoted cell apoptosis.

Influence of miR-431-5p and EPB41L1 expression on invasion and migration of GBM cells

Invasion of GBM cells detected by Transwell assay

In anti-miR and plenti-EPB41L1 groups, the number of U87 cells invaded through the membrane was significantly smaller than that in the control group (Figure 6 A, p < 0.01), but there was no significant difference between control, anti-NC, plenti-NULL and plenti-EPB41L1+miR-mimics groups. In summary, it was proved that down-regulating miR-431-5p expression or up-regulating EPB41L1 expression could both reduce cell invasiveness.

Figure 6

Influence of miR-431-5p and EPB41L1 expression on GBM cell invasion and migration. A – Cell invasiveness of U87 cells in different groups detected by Transwell assay; cell invasiveness in anti-miR and plenti-EPB41L1 groups was compared with that in control group. B – Cell migration of U87 cells in different groups detected by wound healing assay. Compared with anti-miR group

GBM – glioblastoma multiforme; *p < 0.05 compared with anti-miR group, #p < 0.05 compared with plenti-NULL group.

/f/fulltexts/AOMS/37835/AMS-15-37835-g006_min.jpg

Cell migration detected by wound healing assay

The results of the wound healing assay showed that in both anti-miR and plenti-EPB41L1 groups, the scratch width was significantly wider than that in the control group (Figure 6 B). The results indicated that decreasing the expression of miR-431-5p and increasing the expression of EPB41L1 could weaken cell migration.

Discussion

Glioblastoma multiforme is widely accepted to be one of the most common malignant tumors of the primary brain in adults [2326]. Due to the high-level invasiveness, the prognosis is always bad with a high recurrence rate [23]. Therefore, it is of high importance to research the pathogenesis of GBM. Here, in this study, we revealed one of the possible molecular mechanisms whereby miR-431-5p may enhance the invasion and proliferation of GBM cells via suppressing EPB41L1. Through dual luciferase and Western blot assays, we have confirmed this target regulating relationship between GBM and EPB41L1. It is the first time that the target relationship between miR-431-5p and EPB41L1 in GBM cells has been studied.

Many previous studies have come to a conclusion that miRNAs act as key factors in the pathogenesis of many human cancers including gastric cancer [27], ovarian cancer [28], esophageal squamous cancer [29], bladder cancer [30], etc., and they have been considered as one of the most important factors in studies that focus on cancer pathogenesis. As for GBM, many miRNAs seem to be related to its carcinogenesis, such as miR-153 [31], miR-7-1-3p [32], miR-124 [33], and they serve as either tumor suppressors or oncomirs. We herein discovered that miR-431-5p was deregulated in GBM tissues and cells, indicating that it might be associated with GBM carcinogenesis. MiR-431 has been reported to be related to many human diseases including hepatocellular carcinoma [16, 34], spinal muscular atrophy [13] and medulloblastomas [14], etc. As for GBM, Tanaka et al. found that the down-regulation of miR-431 inhibited the viability of GBM cells [14], which is similar to our conclusion that the up-regulation of miR-431-5p could promote the viability of GBM cells. We thus believe that miR-431-5p served as an oncomir in GBM. However, in their research, miR-431 was only regarded as a down-stream target and did not focus on the down-stream target of miR-431. Many previous studies have proved that miRNAs might be mediators and target oncogenes to exert their functions [3537]. Here in our study, we revealed that miR-431-5p could target tumor suppressors and augment the aggressiveness of GBM.

EPB41L1, also known as 4.1N, is a kind of human protein which has been defined to be closely related to ovarian cancer [38, 39] and carcinogenesis in prostate [40]. Also, Wang et al. claimed that EPB41L1 could link PP1 to JNK-c-Jun pathway regulation and this procedure implied that EPB41L1 might act as a potential tumor suppressor in non-small cell lung cancer [17]. Xi et al. [39] took epithelial ovarian cancer as an example and proved that EPB41L1 expression level significantly decreased during the malignant transformation of epithelial ovarian tumors, which can also support our results. Zhang et al. confirmed a similar relationship in ovarian cancer that EPB41L1 could suppress hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer cells [38]. Of all the studies on EPB41L1, we found that EPB41L1 primarily suppressed the proliferation, invasion and transition of cancer cells. And here we reported that the up-regulation of EPB41L1 might suppress the viability of GBM cells.

However, although we confirmed that miR-431-5p could target EPB41L1, and it is the first miRNA that was found to target EPB41L1, we have certain limitations in this study. First, miR-431-5p is not the only regulating factor of EPB41L1. It could be regulated by various factors including calmodulin such as Ca2+/CaM, the K+/Cl cotransporter KCC2, dopamine receptors, and glutamate receptors ionotropic (AMPA) receptors [4145] in a variety of cancers. Second, EPB41L1 is associated with malignancy [39, 46], and miR-431-5p is associated with malignancy [15, 16, 34], but whether the degree of the GBM malignancy has an influence on the effects of miR-431-5p or EPB41L1 needs further confirmation. Thirdly, the target relationship between miR-431-5p and EPB41L1 was found, but we could not exclude the possibility that it is a part of a signaling pathway in the whole pathogenesis of GBM. Previous studies have indicated that a miR-protein regulating relationship might be a part of a signaling pathway regulation [4749]. Thirdly, the deviations caused by age, gender and different periods of the diseases were not included. Further research is still warranted to comprehend the pathogenesis of GBM.

In conclusion, for the first time we reported that miR-431-5p promoted the proliferation and invasion of GBM cells via suppressing EPB41L1 and we have proved it via multiple experiments including Western blot, dual luciferase reporter gene assay, flow cytometry, etc. Our research may provide useful information on the treatment against GBM, and therefore improve the prognosis of the patients.

Conflict of interest

The authors declare no conflict of interest.

References

1 

Wen PY, Kesari S , authors. Malignant gliomas in adults. N Engl J Med. 2008. 359:p. 492–507

2 

Hadjipanayis CG, Van Meir EG , authors. Tumor initiating cells in malignant gliomas: biology and implications for therapy. J Mol Med (Berl). 2009. 87:p. 363–74

3 

Duan R, Han L, Wang Q, et al. , authors. HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-beta pathways. Oncotarget. 2015. 6:p. 27778–93

4 

Stupp R, Hegi ME, Mason WP, et al. , authors. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009. 10:p. 459–66

5 

Stupp R, Mason WP, van den Bent MJ, et al. , authors. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005. 352:p. 987–96

6 

Kouhkan F, Mobarra N, Soufi-Zomorrod M, et al. , authors. MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1. J Med Genet. 2016. 53:p. 24–33

7 

Chekulaeva M, Filipowicz W , authors. Mechanisms of miRNA- mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol. 2009. 21:p. 452–60

8 

Zhang B, Pan X, Cobb GP, Anderson TA , authors. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007. 302:p. 1–12

9 

Ebrahimi A, Sadroddiny E , authors. MicroRNAs in lung diseases: recent findings and their pathophysiological implications. Pulm Pharmacol Ther. 2015. 34:p. 55–63

10 

Qi W, Liang W, Jiang H, Miuyee Waye M , authors. The function of miRNA in hepatic cancer stem cell. Biomed Res Int. 2013. 2013:p. 358902

11 

Zhang S, Zhang H, Zhu J, Zhang X, Liu Y , authors. MiR-522 contributes to cell proliferation of human glioblastoma cells by suppressing PHLPP1 expression. Biomed Pharmacother. 2015. 70:p. 164–9

12 

Xia X, Li Y, Wang W, et al. , authors. MicroRNA-1908 functions as a glioblastoma oncogene by suppressing PTEN tumor suppressor pathway. Mol Cancer. 2015. 14:p. 154

13 

Wertz MH, Winden K, Neveu P, et al. , authors. Cell-type-specific miR-431 dysregulation in a motor neuron model of spinal muscular atrophy. Hum Mol Genet. 2016. 25:p. 2168–81

14 

Tanaka T, Arai M, Jiang X, et al. , authors. Downregulation of microRNA-431 by human interferon-beta inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6. Int J Oncol. 2014. 44:p. 1685–90

15 

Kanaan Z, Roberts H, Eichenberger MR, et al. , authors. A plasma microRNA panel for detection of colorectal adenomas: a step toward more precise screening for colorectal cancer. Ann Surg. 2013. 258:p. 400–8

16 

Sun K, Zeng T, Huang D, et al. , authors. MicroRNA-431 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the ZEB1-mediated epithelial-mensenchymal transition. FEBS Open Bio. 2015. 5:p. 900–7

17 

Wang Z, Ma B, Li H, et al. , authors. Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC. Oncotarget. 2016. 7:p. 509–23

18 

Koljenovic S, Choo-Smith LP, Bakker Schut TC, Kros JM, van den Berge HJ, Puppels GJ , authors. Discriminating vital tumor from necrotic tissue in human glioblastoma tissue samples by Raman spectroscopy. Lab Invest. 2002. 82:p. 1265–77

19 

Zhang W, Bi Y, Li J, et al. , authors. Long noncoding RNA FTX is upregulated in gliomas and promotes proliferation and invasion of glioma cells by negatively regulating miR-342-3p. Lab Invest. 2017. 97:p. 447–57

20 

Kutwin M, Sawosz E, Jaworski S, et al. , authors. Investigation of platinum nanoparticle properties against U87 glioblastoma multiforme. Arch Med Sci. 2017. 13:p. 1322–34

21 

Vlachostergios PJ, Papandreou CN , authors. Efficacy of low dose temozolomide in combination with bortezomib in U87 glioma cells: a flow cytometric analysis. Arch Med Sci. 2015. 11:p. 307–10

22 

Zhao QW, Lin Y, Xu CR, et al. , authors. NDGA-P21, a novel derivative of nordihydroguaiaretic acid, inhibits glioma cell proliferation and stemness. Lab Invest. 2017. 97:p. 1180–7

23 

Zhen L, Li J, Zhang M, Yang K , authors. MiR-10b decreases sensitivity of glioblastoma cells to radiation by targeting AKT. J Biol Res (Thessalon). 2016. 23:p. 14

24 

Wang L, Liu J, Zhong Z, et al. , authors. PTP4A3 is a target for inhibition of cell proliferatin, migration and invasion through Akt/mTOR signaling pathway in glioblastoma under the regulation of miR-137. Brain Res. 2016. 1646:p. 441–50

25 

Liu Y, Xu N, Liu B, et al. , authors. Long noncoding RNA RP11-838N2.4 enhances the cytotoxic effects of temozolomide by inhibiting the functions of miR-10a in glioblastoma cell lines. Oncotarget. 2016. 7:p. 43835–51

26 

Lee H, Hwang SJ, Kim HR, et al. , authors. Neurofibromatosis 2 (NF2) controls the invasiveness of glioblastoma through YAP-dependent expression of CYR61/CCN1 and miR-296-3p. Biochim Biophys Acta. 2016. 1859:p. 599–611

27 

Qiu ZA, He GP , authors. MicroRNA-134 functions as a tumor suppressor gene in gastric cancer. Am J Transl Res. 2016. 8:p. 4320–8

28 

Teng Y, Zuo X, Hou M, et al. , authors. A double-negative feedback interaction between microRNA-29b and DNMT3A/3B contributes to ovarian cancer progression. Cell Physiol Biochem. 2016. 39:p. 2341–52

29 

Wang C, Zhang W, Zhang L, et al. , authors. miR-146a-5p mediates epithelial-mesenchymal transition of oesophageal squamous cell carcinoma via targeting Notch2. Br J Cancer. 2016. 115:p. 1548–54

30 

Wang H, Ke C, Ma X, et al. , authors. MicroRNA-92 promotes invasion and chemoresistance by targeting GSK3beta and activating Wnt signaling in bladder cancer cells. Tumour Biol. 2016. [Epub ahead of print].

31 

Ghasemi A, Fallah S, Ansari M , authors. MiR-153 as a tumor suppressor in glioblastoma multiforme is downregulated by DNA methylation. Clin Lab. 2016. 62:p. 573–80

32 

Chakrabarti M, Ray SK , authors. Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo. Apoptosis. 2016. 21:p. 312–28

33 

Wang R, Zhang S, Chen X, et al. , authors. EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis. Mol Cancer. 2018. 17:p. 166

34 

Pan L, Ren F, Rong M, et al. , authors. Correlation between down-expression of miR-431 and clinicopathological significance in HCC tissues. Clin Transl Oncol. 2015. 17:p. 557–63

35 

Hu HQ, Sun LG, Guo WJ , authors. Decreased miRNA-146a in glioblastoma multiforme and regulation of cell proliferation and apoptosis by target Notch1. Int J Biol Markers. 2016. 31:p. e270–5

36 

Wei F, Wang Q, Su Q, et al. , authors. miR-373 inhibits glioma cell U251 migration and invasion by down-regulating CD44 and TGFBR2. Cell Mol Neurobiol. 2016. 36:p. 1389–97

37 

Yang L, Yan Z, Wang Y, Ma W, Li C , authors. Down-expression of miR-154 suppresses tumourigenesis in CD133(+) glioblastoma stem cells. Cell Biochem Funct. 2016. 34:p. 404–13

38 

Zhang L, Hu A, Li M, et al. , authors. 4.1N suppresses hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer cells. Mol Med Rep. 2016. 13:p. 837–44

39 

Xi C, Ren C, Hu A, et al. , authors. Defective expression of protein 4.1N is correlated to tumor progression, aggressive behaviors and chemotherapy resistance in epithelial ovarian cancer. Gynecol Oncol. 2013. 131:p. 764–71

40 

Schulz WA, Ingenwerth M, Djuidje CE, Hader C, Rahnenführer J, Engers R , authors. Changes in cortical cytoskeletal and extracellular matrix gene expression in prostate cancer are related to oncogenic ERG deregulation. BMC Cancer. 2010. 10:p. 505

41 

Li H, Khirug S, Cai C, et al. , authors. KCC2 interacts with the dendritic cytoskeleton to promote spine development. Neuron. 2007. 56:p. 1019–33

42 

Coleman SK, Cai C, Mottershead DG, Haapalahti JP, Keinänen K , authors. Surface expression of GluR-D AMPA receptor is dependent on an interaction between its C-terminal domain and a 4.1 protein. J Neurosci. 2003. 23:p. 798–806

43 

Binda AV, Kabbani N, Lin R, Levenson R , authors. D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N. Mol Pharmacol. 2002. 62:p. 507–13

44 

Shen L, Liang F, Walensky LD, Huganir RL , authors. Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1N-linked actin cytoskeletal association. J Neurosci. 2000. 20:p. 7932–40

45 

Nunomura W, Takakuwa Y, Parra M, Conboy JG, Mohandas N , authors. Ca(2+)-dependent and Ca(2+)-independent calmodulin binding sites in erythrocyte protein 4.1. Implications for regulation of protein 4.1 interactions with transmembrane proteins. J Biol Chem. 2000. 275:p. 6360–7

46 

Ji Z, Shi X, Liu X, et al. , authors. The membrane-cytoskeletal protein 4.1N is involved in the process of cell adhesion, migration and invasion of breast cancer cells. Exp Ther Med. 2012. 4:p. 736–40

47 

He X, Liu Z, Peng Y, Yu C , authors. MicroRNA-181c inhibits glioblastoma cell invasion, migration and mesenchymal transition by targeting TGF-beta pathway. Biochem Biophys Res Commun. 2016. 469:p. 1041–8

48 

Zhu G, Wang Y, Mijiti M, Wang Z, Wu PF, Jiafu D , authors. Upregulation of miR-130b enhances stem cell-like phenotype in glioblastoma by inactivating the Hippo signaling pathway. Biochem Biophys Res Commun. 2015. 465:p. 194–9

49 

Cai J, Zhao J, Zhang N, et al. , authors. MicroRNA-542-3p suppresses tumor cell invasion via targeting AKT pathway in human astrocytoma. J Biol Chem. 2015. 290:p. 24678–88

Copyright: © 2019 Termedia & Banach. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
 
Quick links
© 2020 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe