title: microRNA-374a suppresses colon cancer progression by directly reducing CCND1 to inactivate the PI3K/AKT pathway.
abstract: microRNA-374a (miR-374a) exhibits oncogenic functions in various tumor types. Here we report that miR-374a suppresses proliferation, invasion, migration and intrahepatic metastasis in colon adenocarcinoma cell lines HCT116 and SW620. Notably, we detected that PI3K/AKT signaling and its downstream cell cycle factors including c-Myc, cyclin D1 (CCND1), CDK4 and epithelial-mesenchymal transition (EMT)-related genes including ZEB1, N-cadherin, Vimentin, Slug, and Snail were all significantly downregulated after miR-374a overexpression. Conversely, cell cycle inhibitors p21 and p27 were upregulated. Expression of E-cadherin was only decreased in HCT116, without any obvious differences observed in SW620 cells. Furthermore, luciferase reporter assays confirmed that miR-374a could directly reduce CCND1. Interestingly, when CCND1 was silenced or overexpressed, levels of pPI3K, pAkt as well as cell cycle and EMT genes were respectively downregulated or upregulated. We examined miR-374a levels by in situ hybridization and its correlation with CCND1 expression in CRC tumor tissues. High miR-374a expression with low level of CCND1 was protective factor in CRC. Together these findings indicate that miR-374a inactivates the PI3K/AKT axis by inhibiting CCND1, suppressing of colon cancer progression.
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.|Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.|Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: Zixi
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: Qiaofen
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.|Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Deng
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.
authors.forename: Xian
authors.initials: X
authors.lastname: Lin
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.
authors.forename: Libo
authors.initials: L
authors.lastname: Li
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, PR China.|Department of Pathology, School of Basic Medicine, Guangzhou Medical College, Guangzhou, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, PR China.|Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C530104:CCND1 protein, human; C587995:MIRN374 microRNA 374, human; D035683:MicroRNAs; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: CCND1; CRC; EMT; PI3K/AKT pathway; miR-374a