miR663a‑TTC22V1 axis inhibits colon cancer metastasis

Tian,Wei; Du,Yantao; Ma,Yuwan; Zhang,Baozhen; Gu,Liankun; Zhou,Jing; Deng,Dajun

doi:10.3892/or.2019.6969

miR663a‑TTC22V1 axis inhibits colon cancer metastasis

Authors:
- Wei Tian
- Yantao Du
- Yuwan Ma
- Baozhen Zhang
- Liankun Gu
- Jing Zhou
- Dajun Deng
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Affiliations: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Etiology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
Published online on: January 16, 2019 https://doi.org/10.3892/or.2019.6969
Pages: 1718-1728
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

An increasing number of studies have demonstrated that microRNAs (miRs) may act as oncogenes or anti‑oncogenes in various types of cancer, including colon cancer (CC). However, the clinical and biological signiﬁcance of miR663a in the prognosis of CC and its underlying molecular mechanisms remain unknown. Using the reverse transcription‑quantitative polymerase chain reaction on CC and surgical margin tissue samples from 172 patients with CC, it was identified that miR663a was significantly downregulated in CC (P<0.001), particularly in metastatic CC (P=0.044). miR663a overexpression inhibited the proliferation and migration/invasion of CC cells in vitro, and also tumor growth and metastasis of CC cells in vivo. Additionally, miR663a target genes were analyzed. Inverse changes in tetratricopeptide repeat domain 22 variant 1 (TTC22V1) in response to alterations in miR663a expression were observed. miR663a decreased the reporter activity of the wild‑type TTC22V1‑3' untranslated region (UTR), but did not decrease that of a 3'UTR mutant. miR663a completely abolished cell migration/invasion induced by TTC22V1 containing the wild‑type 3'UTR sequence, but not that induced by TTC22V1 containing the 3'UTR mutant. An inverse correlation between miR663a and TTC22 mRNA levels was observed in CC tissues. These results suggest that TTC22V1 mRNA is a crucial miR663a target that directly promotes cell migration/invasion. TTC22, which, to the best of our knowledge, has rarely been investigated, is located in the nuclei of epithelial cells in colon stem cell niches at crypt bases, and is significantly downregulated in CC, particularly in non‑metastatic CC. High TTC22V1 expression is a significant poor survival factor for patients with CC. Collectively, the results of the present study suggested that TTC22V1 may be a metastasis‑associated gene and that the miR663a‑TTC22V1 axis inhibited CC metastasis.

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1	Dreher A, Rossing M, Kaczkowski B, Nielsen FC and Norrild B: Differential expression of cellular microRNAs in HPV-11 transfected cells. An analysis by three different array platforms and qRT-PCR. Biochem Biophys Res Commun. 403:357–362. 2010. View Article : Google Scholar : PubMed/NCBI
2	Liang P, Lv C, Jiang B, Long X, Zhang P, Zhang M, Xie T and Huang X: MicroRNA profiling in denatured dermis of deep burn patients. Burns. 38:534–540. 2012. View Article : Google Scholar : PubMed/NCBI
3	Li P, Zhu N, Yi B, Wang N, Chen M, You X, Zhao X, Solomides CC, Qin Y and Sun J: MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and vascular neointimal formation. Circ Res. 113:1117–1127. 2013. View Article : Google Scholar : PubMed/NCBI
4	Miao CG, Shi WJ, Xiong YY, Yu H, Zhang XL, Qin MS, Du CL, Song TW, Zhang B and Li J: MicroRNA-663 activates the canonical Wnt signaling through the adenomatous polyposis coli suppression. Immunol Lett. 166:45–54. 2015. View Article : Google Scholar : PubMed/NCBI
5	Hu W, Xu S, Yao B, Hong M, Wu X, Pei H, Chang L, Ding N, Gao X, Ye C, et al: MiR-663 inhibits radiation-induced bystander effects by targeting TGFB1 in a feedback mode. RNA Biol. 11:1189–1198. 2014. View Article : Google Scholar : PubMed/NCBI
6	Latruffe N, Lançon A, Frazzi R, Aires V, Delmas D, Michaille JJ, Djouadi F, Bastin J and Cherkaoui-Malki M: Exploring new ways of regulation by resveratrol involving miRNAs, with emphasis on inflammation. Ann NY Acad Sci 1348. 97–106. 2015. View Article : Google Scholar
7	Jiao L, Deng Z, Xu C, Yu Y, Li Y, Yang C, Chen J, Liu Z, Huang G, Li LC, et al: miR-663 induces castration-resistant prostate cancer transformation and predicts clinical recurrence. J Cell Physiol. 229:834–844. 2014. View Article : Google Scholar : PubMed/NCBI
8	Yi C, Wang Q, Wang L, Huang Y, Li L, Liu L, Zhou X, Xie G, Kang T, Wang H, et al: MiR-663, a microRNA targeting p21^WAF1/CIP1, promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma. Oncogene. 31:4421–4433. 2012. View Article : Google Scholar : PubMed/NCBI
9	Liang S, Zhang N, Deng Y, Chen L, Zhang Y, Zheng Z, Luo W, Lv Z, Li S and Xu T: miR-663 promotes NPC cell proliferation by directly targeting CDKN2A. Mol Med Rep. 16:4863–4870. 2017. View Article : Google Scholar : PubMed/NCBI
10	Shi Y, Chen C, Yu SZ, Liu Q, Rao J, Zhang HR, Xiao HL, Fu TW, Long H, He ZC, et al: miR-663 suppresses oncogenic function of CXCR4 in glioblastoma. Clin Cancer Res. 21:4004–4013. 2015. View Article : Google Scholar : PubMed/NCBI
11	Li Q, Cheng Q, Chen Z, Peng R, Chen R, Ma Z, Wan X, Liu J, Meng M, Peng Z, et al: MicroRNA-663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF-β1. Oncol Rep. 35:1125–1134. 2016. View Article : Google Scholar : PubMed/NCBI
12	Zang W, Wang Y, Wang T, Du Y, Chen X, Li M and Zhao G: miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer. Mol Cancer. 14:372015. View Article : Google Scholar : PubMed/NCBI
13	Tian W, Du Y, Ma Y, Gu L, Zhou J and Deng D: MALAT1-miR663a negative feedback loop in colon cancer cell functions through direct miRNA-lncRNA binding. Cell Death Dis. 9:8572018. View Article : Google Scholar : PubMed/NCBI
14	Huang W, Li J, Guo X, Zhao Y and Yuan X: miR-663a inhibits hepatocellular carcinoma cell proliferation and invasion by targeting HMGA2. Biomed Pharmacother. 81:431–438. 2016. View Article : Google Scholar : PubMed/NCBI
15	Afonyushkin T, Oskolkova OV and Bochkov VN: Permissive role of miR-663 in induction of VEGF and activation of the ATF4 branch of unfolded protein response in endothelial cells by oxidized phospholipids. Atherosclerosis. 225:50–55. 2012. View Article : Google Scholar : PubMed/NCBI
16	Tili E, Michaille JJ, Adair B, Alder H, Limagne E, Taccioli C, Ferracin M, Delmas D, Latruffe N and Croce CM: Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB, JunD. Carcinogenesis. 31:1561–1566. 2010. View Article : Google Scholar : PubMed/NCBI
17	Acevedo N, Reinius LE, Vitezic M, Fortino V, Söderhäll C, Honkanen H, Veijola R, Simell O, Toppari J, Ilonen J, et al: Age-associated DNA methylation changes in immune genes, histone modifiers and chromatin remodeling factors within 5 years after birth in human blood leukocytes. Clin Epigenetics. 7:342015. View Article : Google Scholar : PubMed/NCBI
18	Allan RK and Ratajczak T: Versatile TPR domains accommodate different modes of target protein recognition and function. Cell Stress Chaperones. 16:353–367. 2011. View Article : Google Scholar : PubMed/NCBI
19	Blatch GL and Lässle M: The tetratricopeptide repeat: A structural motif mediating protein-protein interactions. BioEssays. 21:932–939. 1999. View Article : Google Scholar : PubMed/NCBI
20	Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, et al: Proteomics. Tissue-based map of the human proteome. Science. 347:12604192015. View Article : Google Scholar : PubMed/NCBI
21	Sobin LH and Wittekind Ch: International Union Against Cancer (UICC): TNM classification of malignant tumors. 6th. Wiley; New York: 2002,
22	Marullo M, Zuccato C, Mariotti C, Lahiri N, Tabrizi SJ, Di Donato S and Cattaneo E: Expressed Alu repeats as a novel, reliable tool for normalization of real-time quantitative RT-PCR data. Genome Biol. 11:R92010. View Article : Google Scholar : PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Tian W, Qu L, Meng L, Liu C, Wu J and Shou C: Phosphatase of regenerating liver-3 directly interacts with integrin β1 and regulates its phosphorylation at tyrosine 783. BMC Biochem. 13:222012. View Article : Google Scholar : PubMed/NCBI
25	Ullman TA and Itzkowitz SH: Intestinal inflammation and cancer. Gastroenterology. 140:1807–1816. 2011. View Article : Google Scholar : PubMed/NCBI
26	Liu L, Nishihara R, Qian ZR, Tabung FK, Nevo D, Zhang X, Song M, Cao Y, Mima K, Masugi Y, et al: Association between inflammatory diet pattern and risk of colorectal carcinoma subtypes classified by immune responses to tumor. Gastroenterology. 153:1517–1530.e14. 2017. View Article : Google Scholar : PubMed/NCBI
27	Shivappa N, Godos J, Hébert JR, Wirth MD, Piuri G, Speciani AF and Grosso G: Dietary inflammatory index and colorectal cancer risk - a meta-analysis. Nutrients. 9:92017. View Article : Google Scholar :
28	Pastille E, Frede A, McSorley HJ, Gräb J, Adamczyk A, Kollenda S, Hansen W, Epple M, Buer J, Maizels RM, et al: Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer. PLoS Pathog. 13:e10066492017. View Article : Google Scholar : PubMed/NCBI
29	Biswas S, Davis H, Irshad S, Sandberg T, Worthley D and Leedham S: Microenvironmental control of stem cell fate in intestinal homeostasis and disease. J Pathol. 237:135–145. 2015. View Article : Google Scholar : PubMed/NCBI
30	Consortium CCLE: Cancer Cell Line Encyclopedia Consortium; Genomics of Drug Sensitivity in Cancer Consortium: Pharmacogenomic agreement between two cancer cell line data sets. Nature. 528:84–87. 2015.PubMed/NCBI
31	Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, et al: A pathology atlas of the human cancer transcriptome. Science. 357:3572017. View Article : Google Scholar
32	Aguirre-Gamboa R, Gomez-Rueda H, Martínez-Ledesma E, Martínez-Torteya A, Chacolla-Huaringa R, Rodriguez-Barrientos A, Tamez-Peña JG and Treviño V: SurvExpress: An online biomarker validation tool and database for cancer gene expression data using survival analysis. PLoS One. 8:e742502013. View Article : Google Scholar : PubMed/NCBI
33	Loboda A, Nebozhyn MV, Watters JW, Buser CA, Shaw PM, Huang PS, Van't Veer L, Tollenaar RA, Jackson DB, Agrawal D, et al: EMT is the dominant program in human colon cancer. BMC Med Genomics. 4:92011. View Article : Google Scholar : PubMed/NCBI
34	Sveen A, Agesen TH, Nesbakken A, Rognum TO, Lothe RA and Skotheim RI: Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival. Genome Med. 3:322011. View Article : Google Scholar : PubMed/NCBI