miR-193a-5p-mediated Inhibition of the METTL1/COX-2 axis is critical for Astraga...

연구 요약

miR-193a-5p-mediated Inhibition of the METTL1/COX-2 axis is critical for Astragalin-induced apoptosis in cervical cancer.

Scientific reports 학술지에 발표된 이 연구는 Lee Y, Park SY, Shim BS 외 연구팀이 수행하였습니다.

이 연구는 'miR-193a-5p-mediated Inhibition of the METTL1/COX-2 axis is critical for Astragalin-induced apoptosis in cervical cancer.'에 대한 과학적 분석을 제공합니다.

핵심 내용

Astragalin (kaempferol-3-O-glucoside), a flavonoid from Astragalus membranaceus, has been reported to exert anti-inflammatory, antioxidant, neuroprotective, and antitumor activities. However, its molecular mechanisms in cervical cancer remain largely undefined. In this study, we investigated the apoptotic effects of Astragalin in association with methyltransferase-like protein 1 (METTL1)/cyclooxygenase-2 (COX-2) signaling. Astragalin significantly reduced cell viability in SiHa, CaSki, and HeLa cervical cancer cells, increased the sub-G1 population and TUNEL-positive cells, and decreased pro-poly(ADP-ribose) polymerase (pro-PARP) and procaspase-3 expression in SiHa and CaSki cells. Notably, Astragalin downregulated METTL1 and COX-2 expression, consistent with TCGA data linking METTL1 overexpression to poor prognosis in cervical cancer. Cycloheximide chase assays demonstrated stronger inhibition of METTL1 than COX-2 protein stability, while immunoprecipitation revealed METTL1 binding to COX-2 (a weak but significant positive correlation (r = 0.16), which was disrupted by Astragalin. Mechanistically, Astragalin upregulated miR-193a-5p, and its mimic suppressed METTL1 and COX-2 expression in SiHa cells, whereas its inhibitor restored. Collectively, these findings demonstrate that Astragalin induces apoptosis through miR-193a-5p-mediated inhibition of the METTL1/COX-2 signaling axis, highlighting its potential as a promising antitumor candidate for cervical cancer.

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