title: MicroRNA‑135b regulates the stability of PTEN and promotes glycolysis by targeting USP13 in human colorectal cancers.
abstract: Dysregulation of microRNAs has been reported to be involved in the progression of human colorectal cancers (CRCs). Loss of the adenomatous polyposis coli (APC) gene is a common initiating event in CRCs. PTEN inactivation by mutation or allelic loss also occurs in CRCs. miR‑135b was reported to be upregulated in CRCs and its overexpression was due to APC/β‑catenin and PTEN/PI3K pathway deregulation. APC was proven to be a target of miR‑135b and forms a feedback loop with miR‑135b. In the present study, we found that ubiquitin‑specific peptidase 13 (USP13) was a target of miR‑135b. miR‑135b downregulated the expression of USP13, and reduced the stability of PTEN. miR‑135b promoted cell proliferation and glycolysis that could be reversed by the overexpression of USP13 or PTEN. Moreover, knockdown of USP13 upregulated the levels of endogenous miR‑135b, but not those in CRC cells with PTEN mutation. The results showed positive feedback loops between miR‑135b and PTEN inactivation in CRCs.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation; D010450:Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000235:genetics*; D045325:HCT116 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016415:Sequence Alignment; D064570:Ubiquitin-Specific Proteases; D051176:beta Catenin / Q000378:metabolism
chemical_list: D010450:Endopeptidases; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; D064570:Ubiquitin-Specific Proteases; D051176:beta Catenin; C544965:MIRN135 microRNA, human; C494929:PTEN protein, human; C561638:USP13 protein, human