Department of Cardiology, Xiangya Third Hospital, Central South University, Changsha, 410013, Hunan Province, China.
Lab Invest. 2022 Mar;102(3):253-262. doi: 10.1038/s41374-021-00678-3. Epub 2021 Nov 3.
Cardiac hypertrophy is a common cardiovascular disease that is found worldwide and is characterized by heart enlargement, eventually resulting in heart failure. Exploring the regulatory mechanism of cardiac hypertrophy is beneficial for understanding its pathogenesis and treatment. In our study, we have showed TINCR was downregulated and miR-211-3p was upregulated in TAC- or Ang II-induced models of cardiac hypertrophy. Dual luciferase and RIP assays revealed that TINCR served as a competitive endogenous RNA (ceRNA) for miR-211-3p. Then, we observed that knockdown of miR-211-3p alleviated TAC- or Ang II-induced cardiac hypertrophy both in vivo and in vitro. Mechanistically, we demonstrated that miR-211-3p directly targeted VEGFB and thus regulated the expression of SDF-1α and CXCR4. Rescue assays further confirmed that TINCR suppressed the progression of cardiac hypertrophy by competitively binding to miR-211-3p, thereby enhancing the expression of VEGFB and activating the VEGFB-SDF-1α- CXCR4 signal. Furthermore, overexpression of TINCR suppressed TAC-induced cardiac hypertrophy in vivo by targeting miR-211-3p-VEGFB-SDF-1α- CXCR4 signalling. In conclusion, our research suggests that LncRNA TINCR improves cardiac hypertrophy by targeting miR-211-3p, thus relieving its suppressive effects on the VEGFB-SDF-1α-CXCR4 signalling axis. TINCR and miR-211-3p might act as therapeutic targets for the treatment of cardiac hypertrophy.
心肌肥厚是一种常见的心血管疾病,在全球范围内都有发现,其特征是心脏扩大,最终导致心力衰竭。探讨心肌肥厚的调控机制有助于了解其发病机制和治疗方法。在我们的研究中,我们已经表明,TINCR 在 TAC 或 Ang II 诱导的心肌肥厚模型中下调,miR-211-3p 上调。双荧光素酶和 RIP 测定显示,TINCR 作为 miR-211-3p 的竞争性内源性 RNA(ceRNA)。然后,我们观察到 miR-211-3p 的敲低减轻了体内和体外的 TAC 或 Ang II 诱导的心肌肥厚。机制上,我们证明 miR-211-3p 直接靶向 VEGFB,从而调节 SDF-1α 和 CXCR4 的表达。挽救实验进一步证实,TINCR 通过与 miR-211-3p 竞争结合来抑制心肌肥厚的进展,从而增强 VEGFB 的表达并激活 VEGFB-SDF-1α-CXCR4 信号。此外,TINCR 的过表达通过靶向 miR-211-3p-VEGFB-SDF-1α-CXCR4 信号通路抑制体内 TAC 诱导的心肌肥厚。总之,我们的研究表明,LncRNA TINCR 通过靶向 miR-211-3p 改善心肌肥厚,从而缓解其对 VEGFB-SDF-1α-CXCR4 信号轴的抑制作用。TINCR 和 miR-211-3p 可能是治疗心肌肥厚的潜在治疗靶点。