title: MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell proliferation by directly targeting HMGA2.
abstract: MicroRNAs (miRNAs) are a class of small, single-stranded, non-coding RNA molecules which can act as oncogenes or tumor suppressor genes in human cancer. However, the possible functions and mechanisms of miRNA action in gallbladder cancer (GBC) have not been elucidated. In the present study, it was found that miR-26a was often downregulated in GBC and the expression of miR-26a was associated with neoplasm histological grade. miR-26a significantly inhibited the proliferation of GBC cells based on the gain-of-function assays. Furthermore, we demonstrated that high mobility group AT-hook 2 (HMGA2) was a direct target of miR-26a. The results showed that HMGA2 mRNA levels and miR-26a levels were negatively correlated. In addition, we confirmed that reintroduction of HMGA2 antagonized the inhibition of miR-26a to GBC cell proliferation and all these effects were achieved through the cell cycle. Together, all these results suggest that miR-26a expression contributes to GBC proliferation by targeting HMGA2. miR-26a shows promise as a prognosis factor and therapeutic target of GBC patients.
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Huading
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, School of Medicine, Shanghai 200032, P.R. China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, School of Medicine, Shanghai 200032, P.R. China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, School of Medicine, Shanghai 200032, P.R. China.
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Zha
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, School of Medicine, Shanghai 200032, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, School of Medicine, Shanghai 200032, P.R. China.
authors.forename: Linhui
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Jing'an District Center Hospital of Shanghai Huashan Hospital, Fudan University, Jing'an Branch, Shanghai 200040, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Zongyou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Baobing
authors.initials: B
authors.lastname: Yin
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Baojin
authors.initials: B
authors.lastname: Ma
mesh_terms: D000328:Adult; D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D025743:HMGA2 Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D025743:HMGA2 Protein; D035683:MicroRNAs; C528163:MIRN26 microRNA, human