Long non‑coding RNA MBI‑52 inhibits the development of liver fibrosis by regulating the microRNA‑466g/SMAD4 signaling pathway

Abstract

Liver fibrosis is a wound healing response triggered by liver injury. In severe cases, it may develop into liver cirrhosis, liver cancer and liver failure. Long non-coding RNAs (lncRNAs) play key roles in the development of liver fibrosis. The present study aimed to investigate the role of lncRNA-MBI-52 (lnc-MBI-52) in the progression of liver fibrosis. Carbon tetrachloride (CCl 4 )-induced injury was performed to establish a mouse liver fibrosis model, and exogenous transforming growth factor-β1 was used to establish a hepatic stellate cell (HSC) activation model. Reverse transcription-quantitative PCR and western blot analyses were performed to detect mRNA and protein expression, respectively. RNA pull-down assay was performed to assess the interaction between microRNA (miR)-466g and lnc-MBI-52 or SMAD4. Dual-luciferase reporter assay was performed to verify the target of miR-466g. lnc-MBI-52 was overexpressed in CCl 4 -induced mouse liver fibrosis models and activated HSCs. lnc-MBI-52 knockdown suppressed liver fibrosis in vitro. Moreover, knockdown of lnc-MBI-52 downregulated α-smooth muscle actin and collagen type I expression. In addition, lnc-MBI-52 and SMAD4 were identified as targets of miR-466g. The effects of lnc-MBI-52 on HSC activation were reversed following transfection with miR-466g mimics or SMAD4 knockdown. lnc-MBI-52 miR-466g significantly decreased lnc-MBI-52 expression, while overexpression of lnc-MBI-52 suppressed miR-466g expression. The results of the RNA pull-down assay confirmed the interaction between miR-466g and lnc-MBI-52. Taken together, lnc-MBI-52 induced liver fibrosis by regulating the miR-466g/SMAD4 axis, which may provide a new possible strategy for liver fibrosis.

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…Silencing TUG1 may ameliorate liver 1% DMN induces LF via quelling TGF-β1/Smad signal [22] . Lnc-MBI-52 also induces LF though modulating miR-466g/SMAD4 axis, opening up a new possible bridge to LF [23] . In addition, the potent pro-fibrotic cytokine TGF-β1 was found to promote Lnc-MALAT1 expression, as well as its pro-fibrotic effect was abrogated though Lnc-MALAT1 siRNA, demonstrating Lnc-MALAT1 may act as a vector for HSCs stimulation.…”

Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway

“…Smad4, encoded by the Smad4 gene, is an intracellular transcriptional mediator of the TGFβ signaling pathway, so it can interact with Smad2/3 in cells and mediate the TGF-β signaling pathway ( Li et al, 2022b ). In addition, Smad4, as the only Co-Smad identified in mammals, mediates the signals from TGF-β and bone morphogenetic protein (BMP) signaling pathways and helps them shuttle into the nucleus ( Kamato et al, 2013 ).…”

microRNAs‐based diagnostic and therapeutic applications in liver fibrosis

“…Furthermore, long noncoding RNA (lncRNA) GAS5 inhibits liver fibrosis induced by CCL4, targeting miR‐23a through the PTEN/PI3K/Akt axis (Dong et al, 2019), which was similar to miR‐1297 (X. Luo et al, 2021). miR‐466g/Smad4 axis regulates by Lnc‐MBI‐52 (Y. Li et al, 2022). Study shows that mice BDL or CCL4‐induced liver fibrosis is attenuated by miR‐30a via inhibiting Beclin1‐mediated autophagy (J. Chen et al, 2017).…”

“…miR-466g/Smad4 axis regulates by Lnc-MBI-52 (Y. Li et al, 2022). Study shows that mice BDL or CCL4-induced liver fibrosis is attenuated by miR-30a via inhibiting Beclin1-mediated autophagy (J.…”