Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC).
Hsa-miRNA-875-5p (miR-875-5p) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-875-5p on colorectal carcinoma (CRC) is still ambiguous. In this study, we investigated the role of miR-875-5p on the development of CRC. The results indicated that miR-875-5p was significantly down-regulated in primary tumor tissues and very low levels were found in CRC cell lines. Ectopic expression of miR-875-5p in CRC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-875-5p induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-875-5p inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene EGFR was revealed to be a putative target of miR-875-5p, which was inversely correlated with miR-875-5p expression in CRC. Taken together, our results demonstrated that miR-875-5p played a pivotal role on CRC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic EGFR.
Oncology Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, P. R. China.
Tiening
T
Zhang
Oncology Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, P. R. China.
Xun
X
Cai
Oncology Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, P. R. China.
Qi
Q
Li
Oncology Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, P. R. China.
Peng
P
Xue
Oncology Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, P. R. China.
Zhixiao
Z
Chen
Oncology Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, P. R. China.
Xiao
X
Dong
Oncology Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, P. R. China.
Ying
Y
Xue
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D015854:Up-Regulation
D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; C493964:CDKN1C protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; C000606835:MIRN-875 microRNA, human; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors; C505407:CASP3 protein, human; D053148:Caspase 3
EGFR; apoptosis; colorectal carcinoma (CRC); hsa-miRNA-875-5p (miR-875-5p); proliferation