miR‑873 inhibits colorectal cancer cell proliferation by targeting TRAF5 and TAB1

Gong,Hui; Fang,Lishan; Li,Yifan; Du,Jihui; Zhou,Bei; Wang,Xiu; Zhou,Hekai; Gao,Lingli; Wang,Kaixin; Zhang,Juan

doi:10.3892/or.2018.6199

miR‑873 inhibits colorectal cancer cell proliferation by targeting TRAF5 and TAB1

Authors:
- Hui Gong
- Lishan Fang
- Yifan Li
- Jihui Du
- Bei Zhou
- Xiu Wang
- Hekai Zhou
- Lingli Gao
- Kaixin Wang
- Juan Zhang
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Affiliations: Central Laboratory, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518033, P.R. China, Central Laboratory, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518033, P.R. China, Clinical Laboratory, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518033, P.R. China, Department of Pathology, Shenzhen Nanshan People's Hospital/Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, Guangdong 518033, P.R. China
Published online on: January 8, 2018 https://doi.org/10.3892/or.2018.6199
Pages: 1090-1098
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA-873 (miR‑873) has been reported to be dysregulated in a variety of malignancies, however, the biological function and underlying molecular mechanism of miR‑873 in colorectal cancer (CRC) remain unclear. In the present study we found that the expression levels of miR‑873 were markedly decreased in CRC cell lines and tissues from patients. Statistical analysis revealed that miR‑873 expression was inversely correlated with the disease stage of CRC. Kaplan‑Meier survival analysis revealed that patients with CRC with lower miR‑873 expression had shorter overall survival rates. Additionally, downregulation of miR‑873 enhanced the proliferation of CRC cells, while upregulation of miR‑873 reduced this proliferation. Furthermore, we found that tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) and TGF‑β activated kinase 1 (MAP3K7) binding protein 1 (TAB1) were direct targets of miR‑873 in CRC cells. A luciferase assay revealed that ectopic expression of miR‑873 significantly reduced nuclear factor κB (NF‑κB) luciferase activity, while ectopic expression of miR‑873 inhibitor enhanced luciferase activity, suggesting that downregulation of miR‑873 can activate NF‑κB signaling. Therefore, our findings established a tumor-suppressive role for miR‑873 in the inhibition of CRC progression, which may be employed as a novel prognostic marker and as an effective therapeutic target for CRC.

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1	Haggar FA and Boushey RP: Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 22:191–197. 2009. View Article : Google Scholar : PubMed/NCBI
2	Weng W, Wei Q, Toden S, Yoshida K, Nagasaka T, Fujiwara T, Cai S, Qin H, Ma Y and Goel A: Circular RNA ciRS-7-a promising prognostic biomarker and a potential therapeutic target in colorectal cancer. Clin Cancer Res. 23:3918–3928. 2017. View Article : Google Scholar : PubMed/NCBI
3	Zeng J, Tang ZH, Liu S and Guo SS: Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer. World J Gastroenterol. 23:1780–1786. 2017. View Article : Google Scholar : PubMed/NCBI
4	Deng J, Lei W, Fu JC, Zhang L, Li JH and Xiong JP: Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro. Biochem Biophys Res Commun. 443:789–795. 2014. View Article : Google Scholar : PubMed/NCBI
5	Wieser M, Sauerland S, Arnold D, Schmiegel W and Reinacher-Schick A: Peri-operative chemotherapy for the treatment of resectable liver metastases from colorectal cancer: A systematic review and meta-analysis of randomized trials. BMC Cancer. 10:309–321. 2010. View Article : Google Scholar : PubMed/NCBI
6	Moghimi-Dehkordi B and Safaee A: An overview of colorectal cancer survival rates and prognosis in Asia. World J Gastrointest Oncol. 4:71–75. 2012. View Article : Google Scholar : PubMed/NCBI
7	Karin M and Greten FR: NF-kappaB: Linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 5:749–759. 2005. View Article : Google Scholar : PubMed/NCBI
8	Hayden MS and Ghosh S: Shared principles in NF-kappaB signaling. Cell. 132:344–362. 2008. View Article : Google Scholar : PubMed/NCBI
9	Hoesel B and Schmid JA: The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 12:862013. View Article : Google Scholar : PubMed/NCBI
10	Wu D, Wu P, Zhao L, Huang L, Zhang Z, Zhao S and Huang J: NF-κB expression and outcomes in solid tumors: A systematic review and meta-analysis. Medicine (Baltimore). 94:e16872015. View Article : Google Scholar : PubMed/NCBI
11	Chen Z, Zhao L, Zhao F, Yang G and Wang J: MicroRNA-26b regulates cancer proliferation migration and cell cycle transition by suppressing TRAF5 in esophageal squamous cell carcinoma. Am J Transl Res. 8:1957–1970. 2016.PubMed/NCBI
12	Jiang L, Yu L, Zhang X, Lei F, Wang L, Liu X, Wu S, Zhu J, Wu G, Cao L, et al: miR-892b silencing activates NF-κB and promotes aggressiveness in breast cancer. Cancer Res. 76:1101–1111. 2016. View Article : Google Scholar : PubMed/NCBI
13	Harhaj EW and Dixit VM: Deubiquitinases in the regulation of NF-κB signaling. Cell Res. 21:22–39. 2011. View Article : Google Scholar : PubMed/NCBI
14	Khella HWZ, Daniel N, Youssef L, Scorilas A, Nofech-Mozes R, Mirham L, Krylov SN, Liandeau E, Krizova A, Finelli A, et al: miR-10b is a prognostic marker in clear cell renal cell carcinoma. J Clin Pathol. 70:854–859. 2017. View Article : Google Scholar : PubMed/NCBI
15	Chen J, Wang M, Guo M, Xie Y and Cong YS: miR-127 regulates cell proliferation and senescence by targeting BCL6. PLoS One. 8:e802662013. View Article : Google Scholar : PubMed/NCBI
16	Li M, Wang Y, Song Y, Bu R, Yin B, Fei X, Guo Q and Wu B: MicroRNAs in renal cell carcinoma: A systematic review of clinical implications (Review). Oncol Rep. 33:1571–1578. 2015. View Article : Google Scholar : PubMed/NCBI
17	Zhao G, Cai C, Yang T, Qiu X, Liao B, Li W, Ji Z, Zhao J, Zhao H, Guo M, et al: MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One. 8:e539062013. View Article : Google Scholar : PubMed/NCBI
18	Go H, Jang JY, Kim PJ, Kim YG, Nam SJ, Paik JH, Kim TM, Heo DS, Kim CW and Jeon YK: MicroRNA-21 plays an oncogenic role by targeting FOXO1 and activating the PI3K/AKT pathway in diffuse large B-cell lymphoma. Oncotarget. 6:15035–15049. 2015. View Article : Google Scholar : PubMed/NCBI
19	Li Y, VandenBoom TG II, Kong D, Wang Z, Ali S, Philip PA and Sarkar FH: Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 69:6704–6712. 2009. View Article : Google Scholar : PubMed/NCBI
20	Peng Y, Liu YM, Li LC, Wang LL and Wu XL: microRNA-503 inhibits gastric cancer cell growth and epithelial-to-mesenchymal transition. Oncol Lett. 7:1233–1238. 2014. View Article : Google Scholar : PubMed/NCBI
21	Nofech-Mozes R, Khella HW, Scorilas A, Youssef L, Krylov SN, Lianidou E, Sidiropoulos KG, Gabril M, Evans A and Yousef GM: MicroRNA-194 is a marker for good prognosis in clear cell renal cell carcinoma. Cancer Med. 5:656–664. 2016. View Article : Google Scholar : PubMed/NCBI
22	Rapti SM, Kontos CK, Papadopoulos IN and Scorilas A: High miR-96 levels in colorectal adenocarcinoma predict poor prognosis, particularly in patients without distant metastasis at the time of initial diagnosis. Tumour Biol. 37:11815–11824. 2016. View Article : Google Scholar : PubMed/NCBI
23	Lee TS, Jeon HW, Kim YB, Kim YA, Kim MA and Kang SB: Aberrant microRNA expression in endometrial carcinoma using formalin-fixed paraffin-embedded (FFPE) tissues. PLoS One. 8:e814212013. View Article : Google Scholar : PubMed/NCBI
24	Skalsky RL and Cullen BR: Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene. PLoS One. 6:e242482011. View Article : Google Scholar : PubMed/NCBI
25	Wang RJ, Li JW, Bao BH, Wu HC, Du ZH, Su JL, Zhang MH and Liang HQ: MicroRNA-873 (miRNA-873) inhibits glioblastoma tumorigenesis and metastasis by suppressing the expression of IGF2BP1. J Biol Chem. 290:8938–8948. 2015. View Article : Google Scholar : PubMed/NCBI
26	Chen X, Zhang Y, Shi Y, Lian H, Tu H, Han S, Peng B, Liu W and He X: miR-873 acts as a novel sensitizer of glioma cells to cisplatin by targeting Bcl-2. Int J Oncol. 47:1603–1611. 2015. View Article : Google Scholar : PubMed/NCBI
27	Wu DD, Li XS, Meng XN, Yan J and Zong ZH: MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1. Tumour Biol. 37:10499–10506. 2016. View Article : Google Scholar : PubMed/NCBI
28	Cui J, Bi M, Overstreet AM, Yang Y, Li H, Leng Y, Qian K, Huang Q, Zhang C, Lu Z, et al: miR-873 regulates Erα transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells. Oncogene. 22:1–13. 2014.
29	Gao Y, Xue Q, Wang D, Du M, Zhang Y and Gao S: miR-873 induces lung adenocarcinoma cell proliferation and migration by targeting SRCIN1. Am J Transl Res. 7:2519–2526. 2015.PubMed/NCBI
30	Liao WT, Ye YP, Zhang NJ, Li TT, Wang SY, Cui YM, Qi L, Wu P, Jiao HL, Xie YJ, et al: MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2. J Pathol. 232:415–427. 2014. View Article : Google Scholar : PubMed/NCBI
31	Miao Y, Li J, Qiu X, Li Y, Wang Z and Luan Y: miR-27a regulates the self renewal of the H446 small cell lung cancer cell line in vitro. Oncol Rep. 29:161–168. 2013. View Article : Google Scholar : PubMed/NCBI
32	Li XX, Huang LY, Peng JJ, Liang L, Shi DB, Zheng HT and Cai SJ: Klotho suppresses growth and invasion of colon cancer cells through inhibition of IGF1R-mediated PI3K/AKT pathway. Int J Oncol. 45:611–618. 2014. View Article : Google Scholar : PubMed/NCBI
33	Qu L, Deng B, Zeng Y and Cao Z: Decreased expression of the Nkx2.8 gene correlates with tumor progression and a poor prognosis in HCC cancer. Cancer Cell Int. 14:282014. View Article : Google Scholar : PubMed/NCBI
34	Michael MZ, O' Connor SM, van Holst Pellekaan NG, Young GP and James RJ: Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 1:882–891. 2003.PubMed/NCBI
35	Orang AV and Barzegari A: MicroRNAs in colorectal cancer: From diagnosis to targeted therapy. Asian Pac J Cancer Prev. 15:6989–6999. 2014. View Article : Google Scholar : PubMed/NCBI
36	Kijima T, Hazama S, Tsunedomi R, Tanaka H, Takenouchi H, Kanekiyo S, Inoue Y, Nakashima M, Iida M, Sakamoto K, et al: MicroRNA-6826 and −6875 in plasma are valuable non-invasive biomarkers that predict the efficacy of vaccine treatment against metastatic colorectal cancer. Oncol Rep. 37:23–30. 2017. View Article : Google Scholar : PubMed/NCBI
37	Wang J, Du Y, Liu X, Cho WC and Yang Y: MicroRNAs as regulator of signaling networks in metastatic colon cancer. Biomed Res Int. 2015:8236202015.PubMed/NCBI
38	Amirkhah R, Schmitz U, Linnebacher M, Wolkenhauer O and Farazmand A: MicroRNA-mRNA interactions in colorectal cancer and their role in tumor progression. Genes Chromosomes Cancer. 54:129–141. 2015. View Article : Google Scholar : PubMed/NCBI
39	Ren L, Xiao L, Hu J, Li Z and Wang Z: MDR1 and MDR3 genes and drug resistance to cisplatin of ovarian cancer cells. J Huazhong Univ Sci Technolog Med Sci. 27:721–724. 2007. View Article : Google Scholar : PubMed/NCBI
40	Stordal B, Hamon M, McEneaney V, Roche S, Gillet JP, O'Leary JJ, Gottesman M and Clynes M: Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein. PLoS One. 7:e407172012. View Article : Google Scholar : PubMed/NCBI
41	Hayden MS and Ghosh S: Signaling to NF-kappaB. Genes Dev. 18:2195–2224. 2004. View Article : Google Scholar : PubMed/NCBI
42	Sen R and Baltimore D: Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 46:705–716. 1986. View Article : Google Scholar : PubMed/NCBI
43	Sakamoto K and Maeda S: Targeting NF-kappaB for colorectal cancer. Expert Opin Ther Targets. 14:593–601. 2010. View Article : Google Scholar : PubMed/NCBI
44	Sakamoto K, Maeda S, Hikiba Y, Nakagawa H, Hayakawa Y, Shibata W, Yanai A, Ogura K and Omata M: Constitutive NF-kappaB activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth. Clin Cancer Res. 15:2248–2258. 2009. View Article : Google Scholar : PubMed/NCBI
45	Voboril R and Weberova-Voborilova J: Constitutive NF-kappaB activity in colorectal cancer cells: Impact on radiation-induced NF-kappaB activity, radiosensitivity, and apoptosis. Neoplasma. 53:518–523. 2006.PubMed/NCBI
46	Lind DS, Hochwald SN, Malaty J, Rekkas S, Hebig P, Mishra G, Moldawer LL, Copeland EM III and Mackay S: Nuclear factor-κB is upregulated in colorectal cancer. Surgery. 130:363–369. 2001. View Article : Google Scholar : PubMed/NCBI
47	Wang S, Liu Z, Wang L and Zhang X: NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol. 6:327–334. 2009. View Article : Google Scholar : PubMed/NCBI
48	Vaiopoulos AG, Athanasoula KC and Papavassiliou AG: NF-κB in colorectal cancer. J Mol Med (Berl). 91:1029–1037. 2013. View Article : Google Scholar : PubMed/NCBI