Identification of PAQR3 as a new candidate tumor suppressor in hepatocellular carcinoma

Wu,Hong  Ge; Zhang,Wen  Jie; Ding,Qian; Peng,Gang; Zou,Zhen  Wei; Liu,Ting; Cao,Ru  Bo; Fei,Shi  Jiang; Li,Peng  Cheng; Yang,Kun  Yu; Hu,Jian  Li; Dai,Xiang  Fang; Wu,Gang; Li,Pin  Dong

doi:10.3892/or.2014.3532

December-2014 Volume 32 Issue 6

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December-2014 Volume 32 Issue 6

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Article

Identification of PAQR3 as a new candidate tumor suppressor in hepatocellular carcinoma

Authors:
- Hong Ge Wu
- Wen Jie Zhang
- Qian Ding
- Gang Peng
- Zhen Wei Zou
- Ting Liu
- Ru Bo Cao
- Shi Jiang Fei
- Peng Cheng Li
- Kun Yu Yang
- Jian Li Hu
- Xiang Fang Dai
- Gang Wu
- Pin Dong Li
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Affiliations: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China, Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, P.R. China, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China
Pages: 2687-2695
|
Published online on: October 6, 2014

https://doi.org/10.3892/or.2014.3532
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Abstract

Progestin and adipoQ receptor family member III (PAQR3) is a regulator that negatively modulates the Ras/Raf/MEK/ERK signaling cascade and the GPCR Gβγ subunit signaling pathway. The role of PAQR3 in hepatocellular carcinoma (HCC) has not been elucidated. The present study investigated the expression of PAQR3 and its prognostic value in primary HCC patients. Furthermore, the functional aspects of PAQR3 were also studied using an in vitro cell model. PAQR3 expression was examined in paired HCC and adjacent noncancerous tissues using real-time quantitative RT-PCR (62 pairs) and western blotting (26 pairs). We also analyzed PAQR3 expression in 132 additional HCC samples by immunohistochemistry. The functional impact of PAQR3 on the proliferation and colony formation of an HCC cell line was analyzed by transfecting cells with a full-length PAQR3 expression vector or siRNA targeting PAQR3. The expression of PAQR3 was significantly decreased in the cancer tissues. Clinicopathological analyses showed that the expression of PAQR3 was significantly correlated with expression of serum α-fetoprotein (AFP), mitotic count, tumor size, histological grade and recurrence. Notably, Kaplan-Meier survival curves revealed a correlation between decreased expression of PAQR3 and the poor prognosis of HCC patients. Multivariate analyses showed that PAQR3 expression is an independent prognostic marker for overall and disease-free survival of HCC patients. Furthermore, restoring PAQR3 expression in HCC cells significantly diminished Hep3B cell proliferation and colony formation. Silencing PAQR3 expression in hepatic normal cell line LO2 significantly enhanced cell growth. PAQR3 may play an important role in the progression of HCC and serve as a potential candidate for the targeted therapy of HCC.

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1	Parkin DM, Bray F, Ferlay J, et al: Estimating the world cancer burden: Globocan 2000. Int J Cancer. 94:153–156. 2001. View Article : Google Scholar : PubMed/NCBI
2	He J, Gu D, Wu X, et al: Major causes of death among men and women in China. N Engl J Med. 353:1124–1134. 2005. View Article : Google Scholar : PubMed/NCBI
3	Thomas MB and Zhu AX: Hepatocellular carcinoma: The need for progress. J Clin Oncol. 23:2892–2899. 2005. View Article : Google Scholar : PubMed/NCBI
4	Zender L, Villanueva A, Tovar V, et al: Cancer gene discovery in hepatocellular carcinoma. J Hepatol. 52:921–929. 2010. View Article : Google Scholar : PubMed/NCBI
5	Feng L, Xie X, Ding Q, et al: Spatial regulation of Raf kinase signaling by RKTG. Proc Natl Acad Sci USA. 104:14348–14353. 2007. View Article : Google Scholar : PubMed/NCBI
6	Luo X, Feng L, Jiang X, et al: Characterization of the topology and functional domains of RKTG. Biochem J. 414:399–406. 2008. View Article : Google Scholar : PubMed/NCBI
7	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. 29:1157–1163. 2008. View Article : Google Scholar : PubMed/NCBI
8	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. 29:5404–5415. 2010. View Article : Google Scholar : PubMed/NCBI
9	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. 30:78–90. 2010. View Article : Google Scholar : PubMed/NCBI
10	Wang X, Li X, Fan F, et al: PAQR3 plays a suppressive role in the tumorigenesis of colorectal cancers. Carcinogenesis. 33:2228–2235. 2012. View Article : Google Scholar : PubMed/NCBI
11	Jiang Y, Xie X, Li Z, et al: Functional cooperation of RKTG with p53 in tumorigenesis and epithelial-mesenchymal transition. Cancer Res. 71:2959–2968. 2011. View Article : Google Scholar : PubMed/NCBI
12	Xie X, Zhang Y, Jiang Y, et al: Suppressive function of RKTG on chemical carcinogen-induced skin carcinogenesis in mouse. Carcinogenesis. 29:1632–1638. 2008. View Article : Google Scholar : PubMed/NCBI
13	Grabinski N, Ewald F, Hofmann BT, et al: Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells. Mol Cancer. 20:112012.PubMed/NCBI
14	Psyrri A, Arkadopoulos N, Vassilakopoulou M, et al: Pathways and targets in hepatocellular carcinoma. Expert Rev Anticancer Ther. 12:1347–1357. 2012. View Article : Google Scholar : PubMed/NCBI
15	Jain S, Singhal S, Lee P, et al: Molecular genetics of hepatocellular neoplasia. Am J Transl Res. 2:105–118. 2010.
16	Guichard C, Amaddeo G, Imbeaud S, et al: Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 44:694–698. 2012. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Identification of PAQR3 as a new candidate tumor suppressor in hepatocellular carcinoma

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