MicroRNA-498 disturbs the occurrence and aggression of colon cancer through targeting MDM2 to mediate PPAR? ubiquitination.
MicroRNA (miR)-498 is indicative of diagnostic and prognostic significance in colon cancer (CC). On the basis of that, this study is initiated from miR-498, combined with mouse double minute 2 (MDM2)/peroxisome proliferator-activated receptor ? (PPAR?) ubiquitination axis to have an insight into CC progression.CC tissues and their adjacent tissues were ... harvested to determine miR-498, MDM2 and PPAR? expression. The interactions among these three factors were identified. The screened human CC cells were transfected with miR-498/MDM2-related sequences, followed by detection of the biological behaviors of CC cells. Xenografted tumors were taken to validate cell experimental outcomes. Bioinformatics and dual-luciferase report analysis verified the targeting relationship between miR-498 and MDM2. The relation between MDM2 and PPAR? was identified by immunoprecipitation and in vivo deubiquitination.Down-regulated miR-498 and PPAR? and up-regulated MDM2 were exhibited in CC. miR-498 targeted MDM2 while MDM2 mediated PPAR? ubiquitination. Elevated miR-498 or reduced MDM2 impaired cell viability, colony-forming, migratory and invasive activities and enhanced apoptosis in CC. Elevated MDM2 abolished the effects of up-regulated miR-498 on the biological behaviors of CC cells. Elevated miR-498 or reduced MDM2 depressed tumorigenic ability of CC cells in mice.It is conclusive that restoring miR-498 depresses MDM2 to modify PPAR? ubiquitination, thereby disturbing the tumorigenesis of CC. This work constructs the base for exploring novel agents in treating CC.
Mesh Terms:
Adult, Aged, Aged, 80 and over, Animals, Apoptosis, Carcinogenesis, Cell Line, Tumor, Cell Proliferation, Cell Survival, China, Colonic Neoplasms, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs, Middle Aged, PPAR gamma, Prognosis, Proto-Oncogene Proteins c-mdm2, Transcriptional Activation, Ubiquitination, Xenograft Model Antitumor Assays
Adult, Aged, Aged, 80 and over, Animals, Apoptosis, Carcinogenesis, Cell Line, Tumor, Cell Proliferation, Cell Survival, China, Colonic Neoplasms, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs, Middle Aged, PPAR gamma, Prognosis, Proto-Oncogene Proteins c-mdm2, Transcriptional Activation, Ubiquitination, Xenograft Model Antitumor Assays
Life Sci
Date: Jul. 15, 2021
PubMed ID: 33617858
View in: Pubmed Google Scholar
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