CMTM5 inhibits renal cancer cell growth through inducing cell-cycle arrest and apoptosis

Cai,Bing; Xiao,Yunbei; Li,Yeping; Zheng,Shaobin

doi:10.3892/ol.2017.6350

CMTM5 inhibits renal cancer cell growth through inducing cell-cycle arrest and apoptosis

Authors:
- Bing Cai
- Yunbei Xiao
- Yeping Li
- Shaobin Zheng
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Affiliations: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: June 8, 2017 https://doi.org/10.3892/ol.2017.6350
Pages: 1536-1542
Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CKLF-like MARVEL transmembrane domain-containing 5 (CMTM5) has been reported to function as a potential tumor suppressor in several human cancers. However, the involvement of CMTM5 in human renal cell carcinoma (RCC) remains unclear. The current study aimed to detect its expression pattern in RCC tissues and cells, and to determine its anti‑proliferative functions in this malignancy. The mRNA and protein expression levels of CMTM5 in RCC tissues and cells were detected by reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blotting. Following the transfection with CMTM5 lentivirus or control lenti‑EGFP lentivirus into the RCC cell line ACHN, the viability, migration, apoptosis and cell cycle of these cells were detected by Cell Counting kit‑8 assay, Transwell assay and flow cytometry, respectively. Compared with the adjacent non‑malignant kidney tissue samples, CMTM5 expression was significantly downregulated in RCC tissues (P<0.05). In addition, enforced expression of CMTM5 could efficiently inhibit the cell growth of ACHN cells, which were arrested in G0/G1 phase. Furthermore, the migration and invasion of ACHN cells were also inhibited by restoration of CMTM5 expression. The present data suggest that CMTM5 may function as a tumor suppressor in human RCC by suppressing the viability of RCC cells, implying its potential as a therapeutic target for this malignancy.

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1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Brodaczewska KK, Szczylik C, Fiedorowicz M, Porta C and Czarnecka AM: Choosing the right cell line for renal cell cancer research. Mol Cancer. 15:832016. View Article : Google Scholar : PubMed/NCBI
3	Leibovich BC, Lohse CM, Crispen PL, Boorjian SA, Thompson RH, Blute ML and Cheville JC: Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. J Urol. 183:1309–1315. 2010. View Article : Google Scholar : PubMed/NCBI
4	Grimm MO, Wolff I, Zastrow S, Frohner M and Wirth M: Advances in renal cell carcinoma treatment. Ther Adv Urol. 2:11–17. 2010. View Article : Google Scholar : PubMed/NCBI
5	Xiao W, Wang J, Li H, Guan W, Xia D, Yu G, Xiao H, Lang B, Ma X, Liu J, et al: Fibulin-1 is down-regulated through promoter hypermethylation and suppresses renal cell carcinoma progression. J Urol. 190:291–301. 2013. View Article : Google Scholar : PubMed/NCBI
6	Guo X, Li T, Wang Y, Shao L, Zhang Y, Ma D and Han W: CMTM5 induces apoptosis of pancreatic cancer cells and has synergistic effects with TNF-alpha. Biochem Biophys Res Commun. 387:139–142. 2009. View Article : Google Scholar : PubMed/NCBI
7	Li P, Liu K, Li L, Yang M, Gao W, Feng J, Lv Y, Qu X and Kong B: Reduced CMTM5 expression correlates with carcinogenesis in human epithelial ovarian cancer. Int J Gynecol Cancer. 21:1248–1255. 2011.PubMed/NCBI
8	Niu J, Li H, Zhang Y, Li J, Xie M, Li L, Qin X, Qin Y, Guo X, Jiang Q, et al: Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by promoter methylation in myeloid leukemia. Leuk Res. 35:771–776. 2011. View Article : Google Scholar : PubMed/NCBI
9	Shao L, Cui Y, Li H, Liu Y, Zhao H, Wang Y, Zhang Y, Ng KM, Han W, Ma D and Tao Q: Cmtm5 exhibits tumor suppressor activities and is frequently silenced by methylation in carcinoma cell lines. Clin Cancer Res. 13:5756–5762. 2007. View Article : Google Scholar : PubMed/NCBI
10	Shao L, Guo X, Plate M, Li T, Wang Y, Ma D and Han W: CMTM5-v1 induces apoptosis in cervical carcinoma cells. Biochem Biophys Res Commun. 379:866–871. 2009. View Article : Google Scholar : PubMed/NCBI
11	Xiao Y, Yuan Y, Zhang Y, Li J, Liu Z, Zhang X, Sheng Z, Xu T and Wang X: CMTM5 is reduced in prostate cancer and inhibits cancer cell growth in vitro and in vivo. Clin Transl Oncol. 17:431–437. 2015. View Article : Google Scholar : PubMed/NCBI
12	World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital OrgansEble JN, Sauter G, Epstein JI and Sesterhenn IA: IARC Press; Lyon: pp. 72004
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Dawson MA and Kouzarides T: Cancer epigenetics: From mechanism to therapy. Cell. 150:12–27. 2012. View Article : Google Scholar : PubMed/NCBI
15	Zhang H, Nan X, Li X, Chen Y, Zhang J and Sun L: CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma. Biochem Biophys Res Commun. 447:304–310. 2014. View Article : Google Scholar : PubMed/NCBI
16	Xie J, Yuan Y, Liu Z, Xiao Y, Zhang X, Qin C, Sheng Z, Xu T and Wang X: CMTM3 is frequently reduced in clear cell renal cell carcinoma and exhibits tumor suppressor activities. Clin Transl Oncol. 16:402–409. 2014. View Article : Google Scholar : PubMed/NCBI
17	Su Y, Lin Y, Zhang L, Liu B, Yuan W, Mo X, Wang X, Li H, Xing X, Cheng X, et al: CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer. Cancer Sci. 105:26–34. 2014. View Article : Google Scholar : PubMed/NCBI
18	Plate M, Li T, Wang Y, Mo X, Zhang Y, Ma D and Han W: Identification and characterization of CMTM4, a novel gene with inhibitory effects on hela cell growth through inducing G2/M phase accumulation. Mol Cells. 29:355–361. 2010. View Article : Google Scholar : PubMed/NCBI
19	Sanchez-Pulido L, Martín-Belmonte F, Valencia A and Alonso MA: Marvel: A conserved domain involved in membrane apposition events. Trends Biochem Sci. 27:599–601. 2002. View Article : Google Scholar : PubMed/NCBI
20	Li Z, Xie J, Wu J, Li W, Nie L, Sun X, Sun X, Tang A, Li X, Liu R, et al: CMTM3 inhibits human testicular cancer cell growth through inducing cell-cycle arrest and apoptosis. PloS One. 9:e889652014. View Article : Google Scholar : PubMed/NCBI
21	Li H, Li J, Su Y, Fan Y, Guo X, Li L, Su X, Rong R, Ying J, Mo X, et al: A novel 3p22.3 gene CMTM7 represses oncogenic egfr signaling and inhibits cancer cell growth. Oncogene. 33:3109–3118. 2014. View Article : Google Scholar : PubMed/NCBI
22	Zhang W, Mendoza MC, Pei X, Ilter D, Mahoney SJ, Zhang Y, Ma D, Blenis J and Wang Y: Down-regulation of CMTM8 induces epithelial-to-mesenchymal transition-like changes via c-MET/extracellular signal-regulated kinase (ERK) signaling. J Biol Chem. 287:11850–11858. 2012. View Article : Google Scholar : PubMed/NCBI
23	Clark PE: The role of VHL in clear-cell renal cell carcinoma and its relation to targeted therapy. Kidney Int. 76:939–945. 2009. View Article : Google Scholar : PubMed/NCBI
24	Li C, Liu B, Dai Z and Tao Y: Knockdown of VEGF receptor-1 (VEGFR-1) impairs macrophage infiltration, angiogenesis and growth of clear cell renal cell carcinoma (crcc). Cancer Biol Ther. 12:872–380. 2011. View Article : Google Scholar : PubMed/NCBI