Role of MALAT1 in the Progression of ACLF via the miR-141-3p/TGFB2 Axis and Its Association with Patient Prognosis.

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is implicated in inflammatory responses and is involved in the progression of multiple diseases. The study aimed to investigate the prognostic significance of MALAT1 in acute-on-chronic liver failure (ACLF) patients and explore its potential molecular mechanisms. A total of 150 patients diagnosed with ACLF and 140 healthy individuals were recruited for this study. MALAT1 expression was measured using RT-qPCR. Survival analysis was conducted using the Kaplan-Meier method, while the Cox regression was applied to identify independent risk factors. An in vitro liver injury model was established by inducing the immortalized human hepatocyte line THLE-2 with lipopolysaccharide (LPS). Cell proliferation was assessed using the CCK-8 assay, apoptosis was determined by flow cytometry, and the inflammatory factors were quantified by enzyme-linked immunosorbent assay (ELISA). The dual-luciferase reporter assay was employed to indicate the targeted regulatory interactions. MALAT1 was significantly elevated in ACLF patients, and those with high MALAT1 expression exhibited decreased survival rates. In vitro experiments, LPS induction significantly upregulates MALAT1 expression, while simultaneously downregulating miR-141-3p and upregulating TGFB2 expression. Following MALAT1 inhibition, cell proliferation was significantly enhanced, apoptosis was suppressed, and IL-6 and IL-1β levels were reduced. However, these effects were partially reversed by miR-141-3p inhibition. Moreover, dual-luciferase reporter assays and RNA immunoprecipitation (RIP) experiments suggested that miR-141-3p may directly target TGFB2. Mechanistically, MALAT1 negatively modulated miR-141-3p expression by directly binding to it, thereby alleviating the suppression of its downstream target TGFB2 and contributing to the progression of ACLF. MALAT1 may contribute to ACLF via the MALAT1/miR-141-3p/TGFB2 signaling pathway.