title: miR-302b regulates cell cycles by targeting CDK2 via ERK signaling pathway in gastric cancer.
abstract: To investigate the molecular mechanism of miR-302b in the regulation of cell proliferation and cell cycle regulation in gastric cancer. Samples of tumor and adjacent normal tissues were collected from 30 gastric cancer patients. Bioinformatics and the dual luciferase report were used for verification of the relationship between miR-302b expression and cyclin-dependent kinase 2 (CDK2). RT-PCR and western blot were used to examine CDK2 mRNA and protein levels. The impacts of miR-302b on CDK2 expression and extracellular signal-regulated kinase (ERK) signaling pathway were assessed in cells transfected with miR-302b analogs and CDK2 overexpression carrier, respectively. We used 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) to assay gastric cancer cell growth after transfection, flow cytometry to analyze cell cycle. Compared with normal tissues, miR-302b expression was significantly lower in gastric cancer tissues, which was significantly related to lymph node metastasis, metastasis distance, and TNM staging. miR-302b expression was increased in miR-302b mimics transfected cells and was significantly decreased in miR-302b inhibitors transfected cells. CDK2 is a target gene of miR-302b. Decreased miR-302b and increased CDK2 expressions can significantly promote proliferation and G1/S phase transformation in gastric cancer. miR-302b promoted the proliferation of gastric cancer cells through upregulation of CDK2, thereby inhibiting ERK pathway, which can in turn inhibit the promoting ability of miR-302b on proliferation. The upregulation of miR-302b reduced the expression of CDK2, and inhibited ERK signaling pathway, thereby inhibiting cell proliferation and G1/S phase conversion rate. Therefore, miR-302b provides new perspectives for research of cell regulation and proliferation in gastric cancer, and new targets for gastric cancer diagnosis and treatment.
authors.affiliation: Department of Nursing, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Fu-Yun
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Department of Nursing, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Nursing, Linyi People's Hospital, Linyi, 276003, China. wenping_zh@126.com.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Zhuang
authors.affiliation: Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
authors.forename: Mu-Juan
authors.initials: MJ
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yuan
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D051357:Cyclin-Dependent Kinase 2
keywords: CDK2; ERK; gastric cancer; miR-302b