title: MiR-375 targets KLF4 and impacts the proliferation of colorectal carcinoma.
abstract: MiR-375 has been identified as oncogenes or tumor suppressor genes which has the potential to the development and growth of cancers. However, the limited information concerning the expression and role of miR-375 in colorectal cancer (CRC) is available. In this work, we provide evidence for a function of miR-375 in the inhibition of CRC proliferation. Here, we showed that miR-375, down-modulated in human colorectal cancer tissues compared with normal human colon tissues, including several colorectal cancer cell lines. Subsequently, using the luciferase reporter assays, we found that the KLF4 untranslated region (3'UTR) carries the direct binding site of miR-375. In terms of function in vitro, CCK-8 assay, colony formation assay, and cell cycle assay demonstrated that the overexpression of miR-375 suppressed CRC cell proliferation. Inhibition of KLF4 performed similar effects with miR-375 overexpression on CRC cells, and overexpression of KLF4 could significantly reverse the tumor suppressive effects of miR-375 on CRC cells. Furthermore, we found overexpressed miR-375 effectively repressed tumor growth via KLF4 in xenograft animal experiment. Taken together, these results illustrated that miR-375 depresses proliferation of CRC through regulating 3'UTR of KLF4 mRNA, which might be a promising therapeutic target for treating colorectal cancers.
authors.affiliation: Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China. Qiqi_Mao@hotmail.com.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Quan
authors.affiliation: Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China. zhengqinghui@hotmail.com.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000818:Animals; D063646:Carcinogenesis; D002277:Carcinoma / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D020413:3' Untranslated Regions; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C540933:MIRN375 microRNA, human; D035683:MicroRNAs
keywords: Colorectal cancer; KLF4; MiR-375; Proliferation