环状 RNA TYMP1 通过 microRNA-182A-3p/TGFβ1 轴减少 Smad2/3 磷酸化抑制卵巢癌细胞发生和顺铂耐药性。
Circ TYMP1 Inhibits Carcinogenesis and Cisplatin Resistance in Ovarian Cancer by Reducing Smad2/3 Phosphorylation via a MicroRNA-182A-3p/TGF1B Axis.
机构信息
Department of Gynecological Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin 300100, China.
Research Institute of Obstetrics and Gynecology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin 300100, China.
出版信息
Contrast Media Mol Imaging. 2022 Aug 16;2022:1032557. doi: 10.1155/2022/1032557. eCollection 2022.
TYMP1 is a cancer driver in several human malignancies. However, its significance in ovarian cancer (ovarian carcinoma) remains uncertain. This research aims to understand the TYMP1's role in ovarian carcinoma carcinogenesis and cisplatin (DDP) resistance and its molecular ovarian marchionesses. Circ TYMP1 overexpression in ovarian carcinoma samples led to an accelerated tumor stage. Bioinformatics identified miR-182A-3p as the TYMP1's target transcript. Circ TYMP1 functioned as a sponge for miR-182A-3p, lowering its inhibitory effect on TGF1B. Downregulating circ TYMP1 decreased A2780-Res cell proliferation, invasion, and death resistance. Malignant ovarian carcinoma cells recovered following miR-182A-3p downregulation. TGF1B overexpression boosted A2780-Res cell proliferation, aggression, and cisplatin resistance while reducing Smad2/3 phosphorylation. TYMP1 sequesters miR-182A-3p and promotes TGF1B in ovarian carcinoma, boosting carcinogenesis and cisplatin resistance. This might lead to novel ovarian carcinoma treatments.
TYMP1 是几种人类恶性肿瘤的致癌驱动因子。然而，其在卵巢癌（卵巢癌）中的意义尚不确定。本研究旨在了解 TYMP1 在卵巢癌发生和顺铂（DDP）耐药中的作用及其分子机制。卵巢癌样本中 TYMP1 的circRNA 过表达导致肿瘤分期加速。生物信息学鉴定出 miR-182A-3p 是 TYMP1 的靶转录本。circTYMP1 作为 miR-182A-3p 的海绵，降低了其对 TGF1B 的抑制作用。下调 circTYMP1 可降低 A2780-Res 细胞的增殖、侵袭和耐药性。下调 miR-182A-3p 后，恶性卵巢癌细胞恢复生长。TGF1B 过表达可促进 A2780-Res 细胞的增殖、侵袭和对顺铂的耐药性，同时降低 Smad2/3 磷酸化。TYMP1 可与 miR-182A-3p 结合并促进卵巢癌中的 TGF1B，从而促进肿瘤发生和顺铂耐药。这可能为卵巢癌的治疗提供新的思路。
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