The LINC00657/miR-144-3p/ROCK1 regulatory axis contributed to atrial fibrosis in AF: LINC00657 sponges miR-144-3p to upregulate ROCK1, and silencing LINC00657 attenuated fibrosis and AF inducibility in Ang II-treated cells and mice.
Circulating LINC00657 was elevated in AF patients, discriminated AF from controls, and independently predicted AF risk.
Circulating LINC00657 levels correlated positively with markers of myocardial injury and inflammation in patients.
Ang II upregulated LINC00657 in cardiac fibroblasts, and silencing LINC00657 reduced fibroblast proliferation, inflammation and fibrotic marker expression while promoting apoptosis.
Knockdown of LINC00657 attenuated Ang II-induced atrial fibrosis in mice and improved electrophysiological properties related to AF.
LINC00657 is predominantly cytoplasmic and acts as a ceRNA sponging miR-144-3p, with ROCK1 a direct target of miR-144-3p.
AF patients and model mice showed decreased miR-144-3p and increased ROCK1, correlating negatively and positively with LINC00657, respectively.
Rescue experiments showed the anti-fibrotic effects of LINC00657 silencing depend on miR-144-3p and ROCK1.
The LINC00657/miR-144-3p/ROCK1 axis activates ROCK1/myosin light chain 2 phosphorylation signaling, enhancing actomyosin contractility and stress fiber formation to drive fibrosis.
This study looked at a molecule called LINC00657, a long non-coding RNA (a piece of genetic material that does not make protein but helps regulate other genes), in atrial fibrillation (AF), a common irregular heart rhythm. Atrial fibrosis, or scarring of the upper heart chambers, is thought to help sustain AF. In blood samples from 150 AF patients and 150 matched controls, LINC00657 was higher in AF patients and tracked with markers of heart injury and inflammation. In heart fibroblast cells and in mice given angiotensin II to induce fibrosis, LINC00657 was increased. Turning it down reduced cell growth, inflammation and scar-related proteins, and in mice it reduced atrial scarring, restored a heart electrical property (atrial effective refractory period), and made AF less easily triggered and shorter. The researchers showed that LINC00657 soaks up a small regulatory RNA, miR-144-3p, which normally restrains a protein called ROCK1. Less available miR-144-3p means more ROCK1 activity, which promotes cell contraction and scarring. This research suggests LINC00657 and this pathway could be potential biomarkers or treatment targets for AF-related fibrosis. However, the work involved patient blood samples, rat cells and mice, so it does not show that targeting this pathway would work in people.
Liang X, Ou Z, Wang Y, Yan L. (2026). Long non-coding RNA LINC00657 aggravates atrial fibrosis in atrial fibrillation via the miR-144-3p/ROCK1 competing endogenous RNA axis.. Functional & integrative genomics. https://doi.org/10.1007/s10142-026-02075-9