CircMAST1 inhibits cervical cancer progression by hindering the N4-acetylcytidine modification of YAP mRNA

CircMAST1 通过阻碍 YAP mRNA 的 N4-乙酰胞苷修饰来抑制宫颈癌进展

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作者:Chunyu Zhang #, Li Yuan #, Qiaojian Zou #, Caixia Shao, Yan Jia, Jiaying Li, Yan Liao, Xueyuan Zhao, Weijia Wen, Xu Jing, Guofen Yang, Wei Wang, Hongye Jiang, Shuzhong Yao

Background

Cervical cancer (CCa) is the fourth most common cancer among females, with high incidence and mortality rates. Circular RNAs (circRNAs) are key regulators of various biological processes in cancer. However, the biological role of circRNAs in cervical cancer (CCa) remains largely unknown. This study aimed to elucidate the role of circMAST1 in CCa.

Conclusions

CircMAST1 plays a major suppressive role in the tumor growth and metastasis of CCa. In particular, circMAST1 can serve as a potential biomarker and novel target for CCa.

Methods

CircRNAs related to CCa progression were identified via a circRNA microarray. The relationship between circMAST1 levels and clinicopathological features of CCa was evaluated using the clinical specimens and data of 131 patients with CCa. In vivo and in vitro experiments, including xenograft animal models, cell proliferation assay, transwell assay, RNA pull-down assay, whole-transcriptome sequencing, RIP assay, and RNA-FISH, were performed to investigate the effects of circMAST1 on the malignant behavior of CCa.

Results

CircMAST1 was significantly downregulated in CCa tissues, and low expression of CircMAST1 was correlated with a poor prognosis. Moreover, our results demonstrated that circMAST1 inhibited tumor growth and lymph node metastasis of CCa. Mechanistically, circMAST1 competitively sequestered N-acetyltransferase 10 (NAT10) and hindered Yes-associated protein (YAP) mRNA ac4C modification to promote its degradation and inhibit tumor progression in CCa. Conclusions: CircMAST1 plays a major suppressive role in the tumor growth and metastasis of CCa. In particular, circMAST1 can serve as a potential biomarker and novel target for CCa.

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