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

Xiang, Shijun; Fang, Jie; Wang, Shuyun; Deng, Bingbing; Zhu, Lin

doi:10.3892/or.2014.3694

Cited by 40 publications

(20 citation statements)

References 45 publications

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“…17 Additionally, inhibition of miR-135b in CRC mouse model reduced proliferation, invasion and apoptosis, 18 and miR-135b suppressed the ability of PTEN in CRC. 19 MiR-182 functioned as a key microRNA to promote cell proliferation, metastasis, and drug resistance in cancers according to recent studies. [20][21] In triple-negative breast cancer, knockdown of miR-182 could hinder the cell proliferation.…”

Section: Micrornas (Mirnas) Are a Class Of 19-25 Nucleotides Small Nomentioning

confidence: 99%

“…MiR‐149 has been identified to be correlated with the metastasis and drug resistance to 5‐FU in CRC, and miR‐139‐5p sensitized CRC cell lines to 5‐FU treatment . Additionally, inhibition of miR‐135b in CRC mouse model reduced proliferation, invasion and apoptosis, and miR‐135b suppressed the ability of PTEN in CRC . MiR‐182 functioned as a key microRNA to promote cell proliferation, metastasis, and drug resistance in cancers according to recent studies .…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of microRNA‐135b and microRNA‐182 promotes chemoresistance of colorectal cancer by targeting ST6GALNAC2 via PI3K/AKT pathway

Liu

Zhao

et al. 2017

Molecular Carcinogenesis

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MicroRNAs (miRNAs) are increasingly involved in the development of drug resistance, including 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC). Aberrant sialylation is correlated with human CRC. The study was to explore whether miR-135b and miR-182 modulated 5-FU chemoresistance of CRC by targeting ST6GALNAC2 via PI3K/AKT pathway. MiR-135b and miR-182 were found to be up-regulated in CRC tissues and 5-FU resistant CRC cell lines. Forced miR-135b and miR-182 expression also affected ST6GALNAC2 levels. Using reporter-gene assay, ST6GALNAC2 was identified as direct target of miR-135b and miR-182, while ST6GALNAC2 expression exhibited patterns opposite to that of miR-135b and miR-182 in CRC samples and cell lines. Interestingly, up-regulation of miR-135b or miR-182 increased drug resistance and proliferation, but decreased apoptosis in 5-FU resistant CRC cell lines. Suppression of these miRNAs implicated an inverse function, while altered expression of ST6GALNAC2 mediated CRC progression upon transfection with miR-135b/-182 mimic or inhibitor. Furthermore, miR-135b and miR-182 were clarified to regulate the activity of phosphoinositide-3 kinase (PI3K)/AKT pathway. Inhibition of the PI3K/AKT pathway enhanced the chemosensitivity to 5-FU in HCT-8/5-FU and LoVo/5-FU. Taken together, miR-135b and miR-182 may reverse the resistance to 5-FU in CRC cells by targeting ST6GALNAC2 via PI3K/AKT pathway, which render potential chemotherapy targets for the treatment of CRC.

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Section: Micrornas (Mirnas) Are a Class Of 19-25 Nucleotides Small Nomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulation of microRNA‐135b and microRNA‐182 promotes chemoresistance of colorectal cancer by targeting ST6GALNAC2 via PI3K/AKT pathway

Liu

Zhao

et al. 2017

Molecular Carcinogenesis

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“…Importantly, USP13 protein is downregulated in human breast cancer and correlates with PTEN protein levels [92]. This work identified USP13 as the first DUB that regulates PTEN polyubiquitination and protein stability, which has been independently confirmed by several recent studies [26,93]. Intriguingly, USP13 and a newly identified PTEN deubiquitinase, OTUD3, have a synergistic effect in regulating PTEN, phospho-AKT, and tumor growth in breast cancer [26].…”

Section: Breast Cancer-suppressing Dubsmentioning

confidence: 94%

The role of deubiquitinases in breast cancer

Xiao

Zhang

2016

Cancer Metastasis Rev

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Although growing numbers of oncoproteins and pro-metastatic proteins have been extensively characterized, many of these tumor-promoting proteins are not good drug targets, which represents a major barrier to curing breast cancer and other cancers. There is a need, therefore, for alternative therapeutic approaches to destroying cancer-promoting proteins. The human genome encodes approximately 100 deubiquitinating enzymes (DUBs, also called deubiquitinases), which are amenable to pharmacologic inhibition by small molecules. By removing monoubiquitin or polyubiquitin chains from the target protein, DUBs can modulate the degradation, localization, activity, trafficking, and recycling of the substrate, thereby contributing substantially to the regulation of cancer proteins and pathways. Targeting certain DUBs may lead to destabilization or functional inactivation of some key oncoproteins or prometastatic proteins, including non-druggable ones, which will provide therapeutic benefits to cancer patients. In breast cancer, growing numbers of DUBs are found to be aberrantly expressed. Depending on their substrates, specific DUBs can either promote or suppress mammary tumors. In this article, we review the role and mechanisms of action of DUBs in breast cancer, and discuss the potential of targeting DUBs for cancer treatment.

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“…miR‐135b represses the expression of ubiquitin‐specific peptidase 13 (USP13) and reduces the stability of PTEN in human colorectal cancers (CRCs). Interestingly, knockdown of USP13 increases the levels of endogenous miR‐135b, but not those in CRC cells with PTEN mutation [Xiang et al, ], indicating a positive feedback loop between miR‐135b and PTEN inactivation in CRCs. Furthermore, miRNA‐21 was reported to regulate human telomerase reverse transcriptase (hTERT) expression and control CRC cell growth, and this is mediated via the PTEN/ERK1/2 signaling pathway [Yang et al, ].…”

Section: Function and Regulation Of Ptenmentioning

confidence: 99%

Oncogenic and Therapeutic Targeting of PTEN Loss in Bone Malignancies

Chen

2015

J of Cellular Biochemistry

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Being a tumor suppressor, PTEN functions as a dual-specificity protein and phospholipid phosphatase and regulates a variety of cellular processes and signal transduction pathways. Loss of PTEN function has been detected frequently in different forms of cancers, such as breast, prostate and lung cancer, gastric and colon cancer, skin cancer, as well as endometrial carcinoma. In this review, we provide a summary of PTEN and its role in bone malignancies including bone metastases, multiple myeloma, and osteosarcoma, etc. We highlight the importance of PTEN loss leading to activation of the oncogenic PI3K/Akt/mTOR pathway in tumorigenesis and progression, which can be attributed to both genetic and non-genetic alterations involving gene mutation, loss of heterozygosity, promoter hypermethylation, and microRNA mediated negative regulation. We also discuss the emerging therapeutic applications targeting PTEN loss for the treatment of these bone malignant diseases.

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

Cited by 40 publications

References 45 publications

Upregulation of microRNA‐135b and microRNA‐182 promotes chemoresistance of colorectal cancer by targeting ST6GALNAC2 via PI3K/AKT pathway

Upregulation of microRNA‐135b and microRNA‐182 promotes chemoresistance of colorectal cancer by targeting ST6GALNAC2 via PI3K/AKT pathway

The role of deubiquitinases in breast cancer

Oncogenic and Therapeutic Targeting of PTEN Loss in Bone Malignancies

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