miR-199a/b-3p inhibits HCC cell proliferation and invasion through a novel compensatory signaling pathway DJ-1\Ras\PI3K/AKT

• Published in: Scientific reports Vol. 14; no. 1; p. 224
• Main Authors: Ma, Li-Na, Wu, Li-Na, Liu, Shuai wei, Zhang, Xu, Luo, Xia, Nawaz, Shah, Ma, Zi min, Ding, Xiang-Chun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/114; 631/67; 631/80; 692/308; 692/4028; AKT protein; Apoptosis; Bioinformatics; Carcinoma, Hepatocellular - pathology; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Chromosome 3; Flow cytometry; Gene Expression Regulation, Neoplastic; Genomic imprinting; Humanities and Social Sciences; Humans; Liver Neoplasms - pathology; Luciferases - metabolism; MicroRNAs - genetics; Molecular modelling; multidisciplinary; Neoplastic Processes; PARK7 protein; Phosphatidylinositol 3-Kinases - metabolism; Portal vein; Proteomics; Proto-Oncogene Proteins c-akt - metabolism; Reporter gene; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - genetics; Statistical analysis; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-48760-8

Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC (( P  < 0.001) were closely associated with tumor stage (T), portal vein vascular invasion, OS, DSS, and PFI ( P  < 0.05); miR-199a/b-3p was lowly expressed in HCC ( P  < 0.001), which was the upstream regulator of DJ-1. Spearman coefficient r = −0.113, P  = 0.031; Dual luciferase gene report verified the negative targeting relationship between them P< 0.001; Western blotting demonstrated that miR-199a/b-3p could inhibit the protein expression of DJ-1, Ras and AKT( P  < 0.05); The results of CCK8, cell scratch, Transwell migration and flow cytometry showed that OE + DJ-1 increased the proliferation, migration and invasion ability of HepG2 cells, and decreased the apoptosis process, and the differences were statistically significant ( P  < 0.05), while miR-199a/b-3p had the opposite effect ( P  < 0.05).