环状 RNA 0001052 通过升高 Hipk3 促进心肌肥厚。

Circ_0001052 promotes cardiac hypertrophy via elevating Hipk3.

机构信息

Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.

出版信息

Aging (Albany NY). 2023 Feb 14;15(4):1025-1038. doi: 10.18632/aging.204521.

Cardiac hypertrophy (CH) is a crucial risk factor for sudden death. Circular RNAs (circRNAs) exert significant effects in various biological and pathological processes. Circ_0001052 is sourced from Hipk3 (homeodomain-interacting protein kinase 3) and is reported to aggravate myocardial fibrosis. The purpose of the current study was to clarify the role and mechanism of circ-Hipk3 in CH. Transverse aortic constriction (TAC) was used to create an CH model, and angiotensin II (Ang II) therapy was used to create an CH model in cardiomyocytes (CMs). It was uncovered that circ_0001052 exerted pro-hypertrophic effects in Ang II-treated CMs. Next, the circular characteristics of circ_0001052 were verified, and we identified that circ_0001052 positively regulated Hipk3. Hipk3 exerted the same functions as circ_0001052 did. It is significant to note that circ_0001052 acted as the ceRNA of Hipk3 by sponging miR-148a-3p and miR-124-3p. According to rescue assays, miR-148a-3p and miR-124-3p partially reversed the effects of circ_0001052. Further, we testified that circ_0001052 recruited Srsf1 to stabilize Hipk3. Finally, rescue assays demonstrated that circ_0001052 promoted CH via up-regulation of Hipk3. In conclusion, our work unveiled that circ_0001052 promoted hypertrophic effects through elevating Hipk3 via sponging miR-148a-3p and miR-124-3p and recruiting Srsf1.

心肌肥厚（CH）是猝死的重要危险因素。环状 RNA（circRNA）在各种生物学和病理学过程中发挥重要作用。Circ_0001052 来源于 Hipk3（同源结构域相互作用蛋白激酶 3），据报道可加重心肌纤维化。本研究旨在阐明 circ-Hipk3 在 CH 中的作用和机制。采用横主动脉缩窄（TAC）建立 CH 模型，在心肌细胞（CM）中采用血管紧张素 II（Ang II）治疗建立 CH 模型。结果表明，circ_0001052 在 Ang II 处理的 CMs 中发挥促肥厚作用。接下来，验证了 circ_0001052 的环状特征，发现 circ_0001052 正向调节 Hipk3。Hipk3 发挥与 circ_0001052 相同的功能。值得注意的是，circ_0001052 通过海绵吸附 miR-148a-3p 和 miR-124-3p 作为 Hipk3 的 ceRNA。根据挽救实验，miR-148a-3p 和 miR-124-3p 部分逆转了 circ_0001052 的作用。此外，我们证明 circ_0001052 通过募集 Srsf1 来稳定 Hipk3。最后，挽救实验表明，circ_0001052 通过上调 Hipk3 促进 CH。总之，我们的工作揭示了 circ_0001052 通过海绵吸附 miR-148a-3p 和 miR-124-3p 并募集 Srsf1 来上调 Hipk3 促进肥厚效应。