Dataset Information

Circular RNA circ_0057558 Controls Prostate Cancer Cell Proliferation Through Regulating miR-206/USP33/c-Myc Axis.

ABSTRACT: We previously reported the elevated expression of circ_0057558 in prostate cancer tissues and cell lines. Here, we aimed to determine the biological function of circ_0057558 in prostate cancer. In the current study, circ_0057558 knockdown in prostate cancer cells significantly repressed cell proliferation and colony formation, but promoted cell arrest and enhanced the sensitivity to docetaxel. Bioinformatics analysis prediction and RNA-pull down assay identified miR-206 as the potential binding miRNA of circ_0057558. A negative correlation was observed between the expression of miR-206 and circ_0057558 in prostate cancer tissues. miR-206 mimics rescued the function of circ_0057558 overexpression on prostate cancer cells. Further, the bioinformatics analysis and luciferase assay suggested that miR-206 may target ubiquitin-specific peptidase 33 (USP33). USP33 mRNA expression has negative correlation with miR-206 expression and positive correlation with circ_0057558 expression in prostate cancer tissues. USP33 overexpression partially blocked the effects of miR-206 mimics on prostate cell proliferation. USP33 could bind and deubiquitinate c-Myc. Increased c-Myc protein by circ_0057558 overexpression was partially reversed by miR-206 mimics. The proliferation inhibition activity of MYC inhibitor 361 (MYCi361) was more prominent in primary prostate cancer cells and patient-derived xenograft (PDX) model with higher level of circ_0057558. Collectively, circ_0057558 gives an impetus to cell proliferation and cell cycle control in prostate cancer cell lines by sponging miR-206 and positively regulating the transcription of the miR-206 target gene USP33.

SUBMITTER: Ding T

PROVIDER: S-EPMC7952531 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Circular RNA circ_0057558 Controls Prostate Cancer Cell Proliferation Through Regulating miR-206/USP33/c-Myc Axis.

Ding Tao T Zhu Yanjun Y Jin Huimin H Zhang Ping P Guo Jianming J Zheng Jianghua J

Frontiers in cell and developmental biology 20210226

We previously reported the elevated expression of circ_0057558 in prostate cancer tissues and cell lines. Here, we aimed to determine the biological function of circ_0057558 in prostate cancer. In the current study, circ_0057558 knockdown in prostate cancer cells significantly repressed cell proliferation and colony formation, but promoted cell arrest and enhanced the sensitivity to docetaxel. Bioinformatics analysis prediction and RNA-pull down assay identified miR-206 as the potential binding ...[more]

PMID: 33718387

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Project description:BACKGROUND:Circular RNAs (circRNAs) have emerged as a novel category of non-coding RNA, which exhibit a pivotal effect on regulating gene expression and biological functions, yet how circRNAs function in osteosarcoma (OSA) still demands further investigation. This study aimed at probing into the function of hsa_circ_0000282 in OSA. METHODS:The expressions of circ_0000282 and miR-192 in OSA tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of circ_0000282 and clinicopathological features of OSA patients was analyzed. The expressions of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in OSA cells were assayed by Western blot. The proliferation and apoptosis of OSA cells were examined by CCK-8, BrdU and flow cytometry, respectively. Bioinformatics analysis, dual-luciferase reporter gene assay and RIP experiments were employed to predict and validate the targeting relationships between circ_0000282 and miR-192, and between miR-192 and XIAP, respectively. RESULTS:Circ_0000282 was highly expressed in OSA tissues and cell lines, which represented positive correlation with Enneking stage of OSA patients and negative correlation with tumor differentiation degree. In vitro experiments confirmed that overexpression of circ_0000282 markedly facilitated OSA cell proliferation and repressed cancer cell apoptosis in comparison to control group. Besides, knockdown of circ_0000282 repressed OSA cell proliferation and promoted apoptosis. Additionally, the binding relationships between circ_0000282 and miR-192, and between miR-192 and XIAP were validated. Circ_0000282 indirectly up-regulated XIAP expression by adsorbing miR-192, thereby playing a role in promoting cancer in OSA. CONCLUSION:Circ_0000282 was a novel oncogenic circRNA in OSA. Circ_0000282/miR-192/XIAP axis regulated OSA cell proliferation apoptosis with competitive endogenous RNA mechanism.

Dataset Information

Circular RNA circ_0057558 Controls Prostate Cancer Cell Proliferation Through Regulating miR-206/USP33/c-Myc Axis.

Publications

Circular RNA circ_0057558 Controls Prostate Cancer Cell Proliferation Through Regulating miR-206/USP33/c-Myc Axis.

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