miR‐145 promotes miR‐133b expression through c‐myc and DNMT3A‐mediated methylation in ovarian cancer cells

Li, Jie; Zhang, Songlin; Zou, Yuliang; Wu, Lei; Pei, Meili; Yu, Jiang

doi:10.1002/jcp.29306

“…Many recent studies have found that microRNA is closely related to ovarian cancer [27,28]. Previous studies confirmed that miR-145 regulated different biological functions of ovarian cancer by targeting different target genes [17][18][19][20]. However, the expression pattern and the m6A-regulated role of miR-145 in ovarian cancer were still unclear.…”

Section: Discussionmentioning

confidence: 99%

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

Li

¹

,

Wu

²

,

Pei

³

et al. 2020

Self Cite

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RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC.

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“…Additionally, the miR-145 agomir was able to repress WNT2B expression, and further led to an inhibition of the Wnt/β-catenin signaling in cervical cancer cells [45]. Another research also demonstrated that miR-145 could target c-myc which interacted physically with DNMT3A in ovarian cancer cells, and inhibit the Warburg effect through miR-133b/PKM2 pathways [46]. Similar to previous studies, our results revealed that tanshinone II A increased the expression of miR-145 at mRNA level on HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

Tong

¹

,

Guo

²

,

Yang

³

2020

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Cervical cancer is the fourth most common cancer in women globally. Lack of effective pharmacotherapies for cervical cancer mainly attributed to an elusive understanding of the mechanism underlying its pathogenesis. Pyroptosis plays a key role in inflammation and cancer. Our study identified microRNA (miR) 145 (miR-145)/gasdermin D (GSDMD) signaling pathway as critical mediators in the effect of tanshinone II A on HeLa cells. In the present study, we found that treatment of tanshinone II A led to an obvious repression of cell proliferation and an increase in apoptosis on HeLa cells, especially in high concentration. Compared with the controlled group, tanshinone II A enhanced the activity of caspase3 and caspase9. Notably, the results demonstrated that tanshinone II A regulated cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway. Treatment of tanshinone II A significantly up-regulated the expression of GSDMD and miR-145. After transfection of si-miR-145 plasmids, the effects of tanshinone II A on HeLa cells were converted, including cell proliferation, apoptosis and pyroptosis. In addition, the results showed that tanshinone II A treatment altered the expression level of PI3K, p-Akt, NF-kB p65 and Lc3-I. Collectively, our findings demonstrate that tanshinone II A exerts anticancer activity on HeLa cells by regulating miR-145/GSDMD signaling. The present study is the first time to identify miR-145 as a candidate target in cervical cancer and show an association between miR-145 and pyroptosis, which provides a novel therapy for the treatment of cervical cancer.

show abstract

“…Many recent studies have found that microRNA is closely related to ovarian cancer [27,28]. Previous studies con rmed that miR-145 regulated different biological functions of ovarian cancer by targeting different target genes [17][18][19][20]. However, the expression pattern and the m6A-regulated role of miR-145 in ovarian cancer were still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…MiR-145 has different regulatory genes in different tumors; the molecular mechanisms of tumor suppressors are also different. Previous studies con rmed that miR-145 could regulate different biological functions of ovarian cancer by targeting different target genes [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

Li

¹

,

Wu²,

Pei

³

et al. 2020

Preprint

Self Cite

0

View full text Add to dashboard Cite

RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC.

show abstract

miR‐145 promotes miR‐133b expression through c‐myc and DNMT3A‐mediated methylation in ovarian cancer cells

Cited by 36 publications

References 41 publications

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

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