Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea.
Channelopathy Research Center, Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Republic of Korea.
Cells. 2023 Apr 8;12(8):1114. doi: 10.3390/cells12081114.
Actin dynamics are known to orchestrate various myogenic processes in progenitor cells. Twinfilin-1 (TWF1) is an actin-depolymerizing factor that plays a crucial role in the differentiation of myogenic progenitor cells. However, little is known about the mechanisms underlying the epigenetic regulation of TWF1 expression and impaired myogenic differentiation in the background of muscle wasting. This study investigated how miR-665-3p affects TWF1 expression, actin filaments' modulation, proliferation, and myogenic differentiation in progenitor cells. Palmitic acid, the most prevalent saturated fatty acid (SFA) in food, suppressed TWF1 expression and inhibited the myogenic differentiation of C2C12 cells while increasing the level of miR-665-3p expression. Interestingly, miR-665-3p inhibited TWF1 expression by targeting 3'UTR directly. In addition, miR-665-3p accumulated filamentous actin (F-actin) and enhanced the nuclear translocation of Yes-associated protein 1 (YAP1), consequently promoting cell cycle progression and proliferation. Furthermore, miR-665-3p suppressed the expressions of myogenic factors, i.e., MyoD, MyoG, and MyHC, and consequently impaired myoblast differentiation. In conclusion, this study suggests that SFA-inducible miR-665-3p suppresses TWF1 expression epigenetically and inhibits myogenic differentiation by facilitating myoblast proliferation via the F-actin/YAP1 axis.
肌动蛋白动力学已知在祖细胞中协调各种成肌过程。双丝蛋白-1（TWF1）是一种肌动蛋白解聚因子，在成肌祖细胞的分化中起着关键作用。然而，在肌肉减少症的背景下，TWF1 表达的表观遗传调控和成肌分化受损的机制知之甚少。本研究探讨了 miR-665-3p 如何影响祖细胞中的 TWF1 表达、肌动蛋白丝的调节、增殖和成肌分化。棕榈酸是食物中最常见的饱和脂肪酸（SFA），它抑制 TWF1 的表达，抑制 C2C12 细胞的成肌分化，同时增加 miR-665-3p 的表达水平。有趣的是，miR-665-3p 通过靶向 3'UTR 直接抑制 TWF1 的表达。此外，miR-665-3p 积累丝状肌动蛋白（F-actin）并增强 Yes 相关蛋白 1（YAP1）的核易位，从而促进细胞周期进程和增殖。此外，miR-665-3p 抑制成肌因子的表达，即 MyoD、MyoG 和 MyHC，从而损害成肌细胞分化。总之，本研究表明，SFA 诱导的 miR-665-3p 通过 F-actin/YAP1 轴促进成肌细胞增殖，从而抑制 TWF1 表达的表观遗传调控，并抑制成肌分化。
