MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting 
X-linked inhibitor of apoptosis protein Retraction in /10.3892/or.2022.8280

Han,Jinfeng; Liu,Zhongmin; Wang,Nanya; Pan,Weiyun

doi:10.3892/or.2016.4810

MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein

Retraction in: /10.3892/or.2022.8280

Authors:
- Jinfeng Han
- Zhongmin Liu
- Nanya Wang
- Weiyun Pan
View Affiliations

Affiliations: Department of ICU, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: May 16, 2016 https://doi.org/10.3892/or.2016.4810
Pages: 542-550

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC.

View Figures

View References

1	Meyerhardt JA and Mayer RJ: Systemic therapy for colorectal cancer. N Engl J Med. 352:476–487. 2005. View Article : Google Scholar : PubMed/NCBI
2	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 :
3	Fearon ER and Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 61:759–767. 1990. View Article : Google Scholar : PubMed/NCBI
4	Ying SY, Chang DC, Miller JD and Lin SL: The microRNA: Overview of the RNA gene that modulates gene functions. Methods Mol Biol. 342:1–18. 2006.PubMed/NCBI
5	Maroney PA, Yu Y and Nilsen TW: MicroRNAs, mRNAs, and translation. Cold Spring Harb Symp Quant Biol. 71:531–535. 2006. View Article : Google Scholar
6	Guo H, Ingolia NT, Weissman JS and Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 466:835–840. 2010. View Article : Google Scholar : PubMed/NCBI
7	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
8	McManus MT: MicroRNAs and cancer. Semin Cancer Biol. 13:253–258. 2003. View Article : Google Scholar : PubMed/NCBI
9	Calin GA and Croce CM: MicroRNA-cancer connection: The beginning of a new tale. Cancer Res. 66:7390–7394. 2006. View Article : Google Scholar : PubMed/NCBI
10	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
11	Dong Y, Yu J and Ng SS: MicroRNA dysregulation as a prognostic biomarker in colorectal cancer. Cancer Manag Res. 6:405–422. 2014.PubMed/NCBI
12	Tokarz P and Blasiak J: The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment. Acta Biochim Pol. 59:467–474. 2012.PubMed/NCBI
13	Zhang X, Tang J, Zhi X, Xie K, Wang W, Li Z, Zhu Y, Yang L, Xu H and Xu Z: miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer. Oncotarget. 6:1605–1617. 2015. View Article : Google Scholar : PubMed/NCBI
14	Jiang B, Li Z, Zhang W, Wang H, Zhi X, Feng J, Chen Z, Zhu Y, Yang L, Xu H, et al: miR-874 Inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer. J Gastroenterol. 49:1011–1025. 2014. View Article : Google Scholar
15	Wang L, Gao W, Hu F, Xu Z and Wang F: MicroRNA-874 inhibits cell proliferation and induces apoptosis in human breast cancer by targeting CDK9. FEBS Lett. 588:4527–4535. 2014. View Article : Google Scholar : PubMed/NCBI
16	Kesanakurti D, Maddirela DR, Chittivelu S, Rao JS and Chetty C: Suppression of tumor cell invasiveness and in vivo tumor growth by microRNA-874 in non-small cell lung cancer. Biochem Biophys Res Commun. 434:627–633. 2013. View Article : Google Scholar : PubMed/NCBI
17	Nohata N, Hanazawa T, Kikkawa N, Sakurai D, Fujimura L, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nakagawa M, et al: Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma. Br J Cancer. 105:833–841. 2011. View Article : Google Scholar : PubMed/NCBI
18	Qu Y, Xia P, Zhang S, Pan S and Zhao J: Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin. Oncol Rep. 33:1177–1184. 2015.PubMed/NCBI
19	Sheng L, He P, Yang X, Zhou M and Feng Q: miR-612 negatively regulates colorectal cancer growth and metastasis by targeting AKT2. Cell Death Dis. 6:e18082015. View Article : Google Scholar : PubMed/NCBI
20	Chen Z, Liu S, Tian L, Wu M, Ai F, Tang W, Zhao L, Ding J, Zhang L and Tang A: miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1. Oncotarget. 6:38139–38150. 2015.PubMed/NCBI
21	Ren XL, He GY, Li XM, Men H, Yi LZ, Lu GF, Xin SN, Wu PX, Li YL, Liao WT, et al: MicroRNA-206 functions as a tumor suppressor in colorectal cancer by targeting FMNL2. J Cancer Res Clin Oncol. Oct 29–2015.Epub ahead of print. PubMed/NCBI
22	Nohata N, Hanazawa T, Kinoshita T, Inamine A, Kikkawa N, Itesako T, Yoshino H, Enokida H, Nakagawa M, Okamoto Y, et al: Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma. Br J Cancer. 108:1648–1658. 2013. View Article : Google Scholar : PubMed/NCBI
23	Salvesen GS and Duckett CS: IAP proteins: Blocking the road to death's door. Nat Rev Mol Cell Biol. 3:401–410. 2002. View Article : Google Scholar : PubMed/NCBI
24	Xiang G, Wen X, Wang H, Chen K and Liu H: Expression of X-linked inhibitor of apoptosis protein in human colorectal cancer and its correlation with prognosis. J Surg Oncol. 100:708–712. 2009. View Article : Google Scholar : PubMed/NCBI
25	Connolly K, Mitter R, Muir M, Jodrell D and Guichard S: Stable XIAP knockdown clones of HCT116 colon cancer cells are more sensitive to TRAIL, taxanes and irradiation in vitro. Cancer Chemother Pharmacol. 64:307–316. 2009. View Article : Google Scholar
26	Yamaguchi Y, Shiraki K, Fuke H, Inoue T, Miyashita K, Yamanaka Y, Saitou Y, Sugimoto K and Nakano T: Targeting of X-linked inhibitor of apoptosis protein or survivin by short interfering RNAs sensitize hepatoma cells to TNF-related apoptosis-inducing ligand- and chemotherapeutic agent-induced cell death. Oncol Rep. 14:1311–1316. 2005.PubMed/NCBI
27	Jiang C, Yi XP, Shen H and Li YX: Targeting X-linked inhibitor of apoptosis protein inhibits pancreatic cancer cell growth through p-Akt depletion. World J Gastroenterol. 18:2956–2965. 2012. View Article : Google Scholar : PubMed/NCBI
28	Deveraux QL and Reed JC: IAP family proteins - suppressors of apoptosis. Genes Dev. 13:239–252. 1999. View Article : Google Scholar : PubMed/NCBI
29	Heidelberger C, Chaudhuri NK, Danneberg P, Mooren D, Griesbach L, Duschinsky R, Schnitzer RJ, Pleven E and Scheiner J: Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 179:663–666. 1957. View Article : Google Scholar : PubMed/NCBI
30	Longley DB, Allen WL and Johnston PG: Drug resistance, predictive markers and pharmacogenomics in colorectal cancer. Biochim Biophys Acta. 1766:184–196. 2006.PubMed/NCBI
31	Zhang Y, Talmon G and Wang J: MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer. Cell Death Dis. 6:e18452015. View Article : Google Scholar : PubMed/NCBI
32	Kim SA, Kim I, Yoon SK, Lee EK and Kuh HJ: Indirect modulation of sensitivity to 5-fluorouracil by microRNA-96 in human colorectal cancer cells. Arch Pharm Res. 38:239–248. 2015. View Article : Google Scholar
33	Zhao HJ, Ren LL, Wang ZH, Sun TT, Yu YN, Wang YC, Yan TT, Zou W, He J, Zhang Y, et al: MiR-194 deregulation contributes to colorectal carcinogenesis via targeting AKT2 pathway. Theranostics. 4:1193–1208. 2014. View Article : Google Scholar : PubMed/NCBI