miR-944 inhibits cell migration and invasion by targeting MACC1 in colorectal cancer

Wen,Liqiang; Li,Yingru; Jiang,Zhipeng; Zhang,Yuchao; Yang,Bin; Han,Fanghai

doi:10.3892/or.2017.5611

miR-944 inhibits cell migration and invasion by targeting MACC1 in colorectal cancer

Authors:
- Liqiang Wen
- Yingru Li
- Zhipeng Jiang
- Yuchao Zhang
- Bin Yang
- Fanghai Han
View Affiliations

Affiliations: Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China, Department of Gastroenterology, Hernia and Abdominal Wall Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
Published online on: April 28, 2017 https://doi.org/10.3892/or.2017.5611
Pages: 3415-3422

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

Dysfunction of microRNAs (miRNAs) is strongly proved to participate in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-944 was reported to play either oncogenic or tumor suppressive roles in human cancers. A recent study reported that the levels of miR-944 in recurrent CRC patients were evidently lower than that in non-recurrent cases, suggesting that miR-944 may function as a tumor suppressive miRNA in CRC. Yet, the clinical value and biological function of miR-944 remain rarely known in CRC. In the present study, we present that miR-944 level in CRC tissues is notably reduced compared to matched non-cancerous specimens. Its decreased level is evidently correlated with malignant clinical parameters and poor prognosis of CRC patients. Accordingly, the levels of miR-944 were obviously downregulated in CRC cells. Ectopic expression of miR-944 in CRC cells prominently inhibits the migration and invasion of tumor cells, while miR-944 knockdown increased these effects of CRC cells. Mechanically, miR-944 negatively regulated the metastasis-associated in colon cancer-1 (MACC1) abundance in CRC cells. Herein, MACC1 was found to be a downstream molecule of miR-944 in CRC. An inversely correlation between miR-944 and MACC1 was confirmed in CRC specimens. Furthermore, restoration of MACC1 expression could abrogate the anti-metastatic effects of miR-944 on CRC cells with enhanced cell migration and invasion. MACC1/Met/AKT signaling may be implicated with the function of miR-944 in CRC cells. Altogether, miR-944 potentially act as a prognostic predictor and a drug-target for CRC patients.

View Figures

View References

1	Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
2	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
3	Kloosterman WP and Plasterk RH: The diverse functions of microRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI
4	Zhang W, Dahlberg JE and Tam W: MicroRNAs in tumorigenesis: A primer. Am J Pathol. 171:728–738. 2007. View Article : Google Scholar : PubMed/NCBI
5	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
6	Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI
7	Thomas J, Ohtsuka M, Pichler M and Ling H: MicroRNAs: Clinical Relevance in Colorectal Cancer. Int J Mol Sci. 16:28063–28076. 2015. View Article : Google Scholar : PubMed/NCBI
8	Schultz NA, Andersen KK, Roslind A, Willenbrock H, Wøjdemann M and Johansen JS: Prognostic microRNAs in cancer tissue from patients operated for pancreatic cancer-five microRNAs in a prognostic index. World J Surg. 36:2699–2707. 2012. View Article : Google Scholar : PubMed/NCBI
9	Lazar V, Suo C, Orear C, van den Oord J, Balogh Z, Guegan J, Job B, Meurice G, Ripoche H, Calza S, et al: Integrated molecular portrait of non-small cell lung cancers. BMC Med Genomics. 6:532013. View Article : Google Scholar : PubMed/NCBI
10	Liu M, Zhou K and Cao Y: MicroRNA-944 affects cell growth by targeting EPHA7 in non-small cell lung cancer. Int J Mol Sci. 17:172016. View Article : Google Scholar
11	Ma J, Mannoor K, Gao L, Tan A, Guarnera MA, Zhan M, Shetty A, Stass SA, Xing L and Jiang F: Characterization of microRNA transcriptome in lung cancer by next-generation deep sequencing. Mol Oncol. 8:1208–1219. 2014. View Article : Google Scholar : PubMed/NCBI
12	Powrózek T, Krawczyk P, Kowalski DM, Winiarczyk K, Olszyna-Serementa M and Milanowski J: Plasma circulating microRNA-944 and microRNA-3662 as potential histologic type-specific early lung cancer biomarkers. Transl Res. 166:315–323. 2015. View Article : Google Scholar : PubMed/NCBI
13	Xie H, Lee L, Scicluna P, Kavak E, Larsson C, Sandberg R and Lui WO: Novel functions and targets of miR-944 in human cervical cancer cells. Int J Cancer. 136:E230–E241. 2015. View Article : Google Scholar : PubMed/NCBI
14	Warnecke-Eberz U, Chon SH, Hölscher AH, Drebber U and Bollschweiler E: Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: Comparison of miRNA profiles of exosomes and matching tumor. Tumour Biol. 36:4643–4653. 2015. View Article : Google Scholar : PubMed/NCBI
15	Flores-Pérez A, Marchat LA, Rodríguez-Cuevas S, Bautista VP, Fuentes-Mera L, Romero-Zamora D, Maciel-Dominguez A, de la Cruz OH, Fonseca-Sánchez M, Ruíz-García E, et al: Suppression of cell migration is promoted by miR-944 through targeting of SIAH1 and PTP4A1 in breast cancer cells. BMC Cancer. 16:3792016. View Article : Google Scholar : PubMed/NCBI
16	Christensen LL, Tobiasen H, Holm A, Schepeler T, Ostenfeld MS, Thorsen K, Rasmussen MH, Birkenkamp-Demtroeder K, Sieber OM, Gibbs P, et al: COLOFOL steering group: MiRNA-362-3p induces cell cycle arrest through targeting of E2F1, USF2 and PTPN1 and is associated with recurrence of colorectal cancer. Int J Cancer. 133:67–78. 2013. View Article : Google Scholar : PubMed/NCBI
17	Tu K, Yang W, Li C, Zheng X, Lu Z, Guo C, Yao Y and Liu Q: Fbxw7 is an independent prognostic marker and induces apoptosis and growth arrest by regulating YAP abundance in hepatocellular carcinoma. Mol Cancer. 13:1102014. View Article : Google Scholar : PubMed/NCBI
18	Arlt F and Stein U: Colon cancer metastasis: MACC1 and Met as metastatic pacemakers. Int J Biochem Cell Biol. 41:2356–2359. 2009. View Article : Google Scholar : PubMed/NCBI
19	Stein U, Walther W, Arlt F, Schwabe H, Smith J, Fichtner I, Birchmeier W and Schlag PM: MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med. 15:59–67. 2009. View Article : Google Scholar : PubMed/NCBI
20	Birchmeier C, Birchmeier W, Gherardi E and Woude GF Vande: Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 4:915–925. 2003. View Article : Google Scholar : PubMed/NCBI
21	Chi Y and Zhou D: MicroRNAs in colorectal carcinoma - from pathogenesis to therapy. J Exp Clin Cancer Res. 35:432016. View Article : Google Scholar : PubMed/NCBI
22	Muhammad S, Kaur K, Huang R, Zhang Q, Kaur P, Yazdani HO, Bilal MU, Zheng J, Zheng L and Wang XS: MicroRNAs in colorectal cancer: Role in metastasis and clinical perspectives. World J Gastroenterol. 20:17011–17019. 2014. View Article : Google Scholar : PubMed/NCBI
23	Yan S, Cao Y and Mao A: MicroRNAs in colorectal cancer: Potential biomarkers and therapeutic targets. Front Biosci (Landmark Ed). 20:1092–1103. 2015. View Article : Google Scholar : PubMed/NCBI
24	Liu X, Ji Q, Fan Z and Li Q: Cellular signaling pathways implicated in metastasis of colorectal cancer and the associated targeted agents. Future Oncol. 11:2911–2922. 2015. View Article : Google Scholar : PubMed/NCBI