title: Up-regulation of microRNA-302a inhibited the proliferation and invasion of colorectal cancer cells by regulation of the MAPK and PI3K/Akt signaling pathways.
abstract: Aberrant expression of microRNA-302a (miR-302a) has been frequently reported in some cancers excluding colorectal cancer (CRC). However, the role of miR-302a in CRC has not been reported. In this paper, we examined the effect of miR-302a overexpression on proliferation and invasion in CRC cells. The mRNA level of miR-302a in CRC cell lines was determined by real-time PCR. The miR-302a mimic was transiently transfected into CRC cells using Lipofectamine™ 2000 reagent. Subsequently, cell proliferation and invasion were assessed by MTT and Transwell assays. Western blot and ELISA assay were used to detect the expressions and secretions of matrix metalloproteinases (MMPs). Moreover, the expressions of epithelial marker, mesenchymal markers and transcription factors were also determined by Western blot. In addition, the effects of miR-302a overexpression on the MAPK and PI3K/Akt signaling pathways were investigated by Western blot. Our results showed that the mRNA level of miR-302a was remarkably decreased in CRC cell lines compared with normal colon epithelium cells. Up-regulation of miR-302a inhibited the proliferation and invasion of CRC cells. The expressions and secretions of MMP-9 and -2 were evidently reduced by increasing miR-302a. Besides, we found a decrease of β-catenin, fibronection, vimentin, Snail, Slug, ZEB1 and ZEB2 expressions and an increase of E-cadherin expression. We also found that miR-302a overexpression might decrease the phosphorylation of Erk1/2 and Akt. Altogether, our results indicated that miR-302a overexpression was shown to inhibit proliferation and invasion of CRC cells by reducing the expressions of related proteins through suppressing the MAPK and PI3K/Akt signaling pathways.
authors.affiliation: The First Department of Tumor Surgery, Cangzhou Central Hospital Cangzhou 061001, Hebei Province, People's Republic of China.
authors.forename: Zhi-Jiang
authors.initials: ZJ
authors.lastname: Wei
authors.affiliation: Liver Disease Digestive Center, Beijing Youan Hospital Capital Medical University Beijing 100069, People's Republic of China.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Tao
authors.affiliation: The First Department of Tumor Surgery, Cangzhou Central Hospital Cangzhou 061001, Hebei Province, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The First Department of Tumor Surgery, Cangzhou Central Hospital Cangzhou 061001, Hebei Province, People's Republic of China.
authors.forename: Guo-Da
authors.initials: GD
authors.lastname: Han
authors.affiliation: Department of Radiotherapy, Cangzhou Central Hospital Cangzhou 061001, Hebei Province, People's Republic of China.
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Cangzhou Central Hospital Cangzhou 061001, Hebei Province, People's Republic of China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Miao
authors.affiliation: Department of General Surgery, Cangzhou Central Hospital Cangzhou 061001, Hebei Province, People's Republic of China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Oncology, Beijing University of Chinese Medicine East Hospital Beijing 100078, People's Republic of China.
authors.forename: Zhan-Bing
authors.initials: ZB
authors.lastname: Qiao
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: MAPK signaling pathway; MicroRNA-302a; PI3K/Akt signaling pathway; colorectal cancer; invasion; proliferation