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
SCImago Journal & Country Rank
vol. 14
Basic research

PAQR3 inhibits proliferation via suppressing PI3K/AKT signaling pathway in non-small cell lung cancer

Xiaohui Li, Mengfei Li, Dong Chen, Gongning Shi, Hui Zhao

Arch Med Sci 2018; 14, 6: 1289–1297
Online publish date: 2017/12/13
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Lung cancer is the leading cause of cancer-related death worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. PAQR (progestin and adipoQ receptor family) 3, a Golgi-anchored membrane protein, has been demonstrated to act as a tumor suppressor in multiple cancers. However, the expression and role of PAQR3 have never been explored in NSCLC. The purpose of this study was to investigate the expression and role of PAQR3 in NSCLC.

Material and methods
Expression of PAQR3 at mRNA and protein levels was determined by qRT-PCR and western blot, respectively. Cell proliferation was analyzed by MTT assay. Apoptosis and cell cycle distribution were evaluated by flow cytometry.

The expression of PAQR3 was downregulated in NSCLC tissue samples and cell lines at both mRNA and protein levels (p < 0.05). Overexpression of PAQR3 significantly inhibited cell proliferation, induced apoptosis and promoted cell cycle arrest at G0/G1 phase in NSCLC cell lines (p < 0.05). In contrast, knockdown of PAQR3 showed a reverse effect on NSCLC cells (p < 0.05). Moreover, PAQR3 may exert its tumor suppressive roles via suppressing the PI3K/AKT signaling pathway in NSCLC.

Our findings suggest that PAQR3 is a tumor suppressor in the development of NSCLC and may serve as a novel therapeutic target in the treatment of patients with NSCLC.


NSCLC, PAQR3, proliferation, PI3K/AKT

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108.
Subramaniam S, Thakur RK, Yadav VK, Nanda R, Chowdhury S, Agrawal A. Lung cancer biomarkers: state of the art. J Carcinog 2013; 12: 3.
Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M. Non-small cell lung cancer: genetic predictors. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 2013; 157: 125-36.
Ramnath N, Dilling TJ, Harris LJ, et al. Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143 (5 Suppl): e314S-40S.
Tang YT, Hu T, Arterburn M, et al. PAQR proteins: a novel membrane receptor family defined by an ancient 7-transmembrane pass motif. J Mol Evol 2005; 61: 372-80.
Luo X, Feng L, Jiang X, et al. Characterization of the topology and functional domains of RKTG. Biochem J
2008; 414: 399-406.
Jiang Y, Xie X, Zhang Y, et al. Regulation of G-protein signaling by RKTG via sequestration of the G betagamma subunit to the Golgi apparatus. Mol Cell Biol 2010; 30: 78-90.
Tang SL, Gao YL, Hu WZ. PAQR3 inhibits the proliferation, migration and invasion in human glioma cells. Biomed Pharmacother 2017; 92: 24-32.
Guo W, You X, Xu D, et al. PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells. Carcinogenesis 2016; 37: 397-407.
Huang W, Guo W, You X, et al. PAQR3 suppresses the proliferation, migration and tumorigenicity of human prostate cancer cells. Oncotarget 2016; 8: 53948-58.
Feng L, Xie X, Ding Q, et al. Spatial regulation of Raf kinase signaling by RKTG. Proc Natl Acad Sci USA 2007; 104: 14348-53.
Fan F, Feng L, He J, et al. RKTG sequesters B-Raf to the Golgi apparatus and inhibits the proliferation and tumorigenicity of human malignant melanoma cells. Carcinogenesis 2008; 29: 1157-63.
Wang X, Wang L, Zhu L, et al. PAQR3 modulates insulin signaling by shunting phosphoinositide 3-kinase p110alpha to the Golgi apparatus. Diabetes 2013; 62: 444-56.
Zhang Y, Jiang X, Qin X, et al. RKTG inhibits angiogenesis by suppressing MAPK-mediated autocrine VEGF signaling and is downregulated in clear-cell renal cell carcinoma. Oncogene 2010; 29: 5404-15.
Wu HG, Zhang WJ, Ding Q, et al. Identification of PAQR3 as a new candidate tumor suppressor in hepatocellular carcinoma. Oncol Rep 2014; 32: 2687-95.
Ma Z, Wang Y, Piao T, et al. The tumor suppressor role of PAQR3 in osteosarcoma. Tumour Biol 2015; 36: 3319-24.
Wang X, Li X, Fan F, et al. PAQR3 plays a suppressive role in the tumorigenesis of colorectal cancers. Carcinogenesis 2012; 33: 2228-35.
Xie X, Zhang Y, Jiang Y, et al. Suppressive function of RKTG on chemical carcinogen-induced skin carcinogenesis in mouse. Carcinogenesis 2008; 29: 1632-8.
Liu JY, Wu XY, Wu GN, Liu FK, Yao XQ. FOXQ1 promotes cancer metastasis by PI3K/AKT signaling regulation in colorectal carcinoma. Am J Transl Res 2017; 9: 2207-18.
Yin K, Wang L, Zhang X, et al. Netrin-1 promotes gastric cancer cell proliferation and invasion via the receptor neogenin through PI3K/AKT signaling pathway. Oncotarget 2017; 8: 51177-89.
Xia H, Li Y, Lv X. MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated PI3K/AKT pathway in human non-small lung cancer. Int J Oncol 2016; 49: 1325-33.
Mayer IA, Arteaga CL. The PI3K/AKT pathway as a target for cancer treatment. Ann Rev Med 2016; 67: 11-28.
Chang L, Graham PH, Ni J, et al. Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance. Crit Rev Oncol Hematol 2015; 96: 507-17.
Hu K, Dai HB, Qiu ZL. mTOR signaling in osteosarcoma: oncogenesis and therapeutic aspects (review). Oncol Rep 2016; 36: 1219-25.
King D, Yeomanson D, Bryant HE. PI3King the lock: targeting the PI3K/Akt/mTOR pathway as a novel therapeutic strategy in neuroblastoma. J Pediatr Hematol Oncol 2015; 37: 245-51.
Zhao JJ, Chen PJ, Duan RQ, Li KJ, Wang YZ, Li Y. miR-630 functions as a tumor oncogene in renal cell carcinoma. Arch Med Sci 2016; 12: 473-8.
Zhang C, Li S, Qiao B, et al. CtBP2 overexpression is associated with tumorigenesis and poor clinical outcome of prostate cancer. Arch Med Sci 2015; 11: 1318-23.
Quick links
© 2018 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe