Impacts of miR-145-5p on Proliferation and Apoptosis of Keloid Fibroblasts by Targeting XBP1

This article explores the effect of miR-145-5p targeting XBP1 (endoplasmic reticulum stressrelated protein splicing X-box binding protein 1) on the proliferation and apoptosis of human scar tissue fibroblasts. Human KFBs (keloid fibroblasts) were selected as the research subjects and randomly assigned into Control group (conventional culture), miR-NC group (transfected with miR-NC), miR-145-5p mimics group (transfected with miR-145-5p mimics), miR-145-5p mimics+pcDNA-NC group (transfected with miR-145-5p mimics+pcDNA-NC), miR-145-5p mimics+pcDNA-XBP1 group (transfected with miR-145-5p mimics+pcDNA-XBP1), and human NFB (normal skin fibroblasts) were also used as the NFB group. CCK8 was used to detect cell proliferation. Scratch experiment was used to detect cell migration. Flow cytometry was used to detect cell apoptosis rate. qPCR was used to detect the expression of miR-145-5p and XBP1 mRNA in cells. Western blot was used to detect the expression of Col-I, Col-III, P21, Bax, and XBP1 proteins in cells. In addition, dual luciferase assay was used to detect the interaction between miR-145-5p and XBP1. A patient-derived xenotransplantation model was established, and miR-145-5p mimics and pcDNA-XBP1 were used to intervene, and the growth, apoptosis and Col-I expression of mouse implants were observed. The results showed that compared with NFB group, control group showed a decrease in miR- 145-5p (P<0.05) and a great increase in XBP1 mRNA (P<0.05). Compared with Control group and miR-NC group, the miR-145-5p mimics group showed increased miR-145-5p expression, P21, Bax proteins expression, and apoptosis rate (P<0.05), while decreased XBP1 mRNA, survival rate, clone number, scratch healing rate, and Col-I, Col-III, XBP1 proteins expression (P<0.05). Compared with the miR-145-5p mimics+pcDNA-NC group, the miR-145-5p mimics+pcDNA-XBP1 group showed an increase in XBP1 mRNA, survival rate, clone number, scratch healing rate, and Col-I, Col-III, XBP1 proteins expression (P<0.05), while a decrease in P21 and Bax proteins expression and apoptosis rate (P<0.05). miR-145-5p could target the negative regulation of XBP1 (P<0.05). Overexpression of miR-145-5p inhibited the proliferation and Col-I expression, and induced apoptosis of KFB in vivo, and up-regulation of XBP1 weakened the effects of overexpression of miR-145-5p on the proliferation and apoptosis of KFB in vivo (P<0.05). In

conclusion, miR-145-5p may inhibit KFB cell proliferation and promote cell apoptosis by targeting XBP1 expression.

CSTR: 32200.14.cjcb.2025.07.0015