title: miR-449a promotes liver cancer cell apoptosis by downregulation of Calpain 6 and POU2F1.
abstract: Our previous study shows that Calpain 6 (CAPN6) expression is regulated by PI3K-Akt in liver cancer through POU2F1 and CAPN6 which promote cell proliferation and inhibit apoptosis of liver cancer cells. microRNAs (miRNAs) plays important roles in regulation of gene expression. However, whether miRNAs regulates CAPN6 expression and its cellular function is still unknown. This study aims to investigate how miRNAs regulate liver cancer apoptosis through POU2F1-CAPN6. It was verified that POU2F1 could promote cell proliferation and inhibit apoptosis through CAPN6. Using methods of bioinformatics, miR-449a was predicted as a potential regulator of both CAPN6 and POU2F1. It was verified that CAPN6 and POU2F1 were the target genes of miR-449a by luciferase assay. CAPN6 and POU2F1 protein and mRNA levels decreased in liver cancer cells with miR-449a overexpression using western blot and real time RT-PCR assays. miR-449a expression was lower in liver cancer tissues compared with their normal ones, so did the cells. Overexpression of miR-449a inhibited cell proliferation, induced G1 phase arrest and cell apoptosis in liver cancer. Further research demonstrated that miR-449a inhibited cancer cell proliferation and induced apoptosis via suppressing both POU2F1 and CAPN6. The study indicated that miR-449a functions as a tumor inhibitor in liver cancer by decreasing POU2F1 and CAPN6 expression in liver cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Research Center of Linyi People Hospital, Linyi, Shandong, China.
authors.forename: Yonglei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Linyi People Hospital, Linyi, Shandong, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Chuanzhong
authors.initials: C
authors.lastname: Mei
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zengxia
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; C000622728:CAPN6 protein, human; D002154:Calpain
keywords: CAPN6; apoptosis; liver cancer; miR-449a; proliferation