MicroRNA‑135b regulates the stability of PTEN and promotes glycolysis by targeting USP13 in human colorectal cancers

Xiang,Shijun; Fang,Jiaqing; Wang,Shuyun; Deng,Biao; Zhu,Lin

doi:10.3892/or.2014.3694

MicroRNA‑135b regulates the stability of PTEN and promotes glycolysis by targeting USP13 in human colorectal cancers

Authors:
- Shijun Xiang
- Jiaqing Fang
- Shuyun Wang
- Biao Deng
- Lin Zhu
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Affiliations: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China, Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
Published online on: December 23, 2014 https://doi.org/10.3892/or.2014.3694
Pages: 1342-1348

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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.

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