Fibroblasts and skin tissues of patients with SSc showed high expression of lncHOTAIR, a potential factor involved in SSc development that drives the profibrotic activation of dermal fibroblasts via the enhancer of zeste 2 (EZH2)/miR-34a/NOTCH/collagen/α-SMA pathway. Here, ACTA1 is linked to systemic sclerosis.