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Let-7 miRNAs and isoforms of miR-203a involve in regulation of colon cancer metastasis by receptor CD44

ABSTRACT: Metastasis formation represents a formidable challenge to oncologists due to limits the survival of colorectal cancer (CRC) patients. Recently we demonstrated that CD44 promotes spontaneous distant metastasis in a CRC xenograft model through primary tumor-related effects. The depletion of CD44 was associated with reduction in hypoxia, EMT, and improved mitochondrial metabolism. Together these effects limit the metastatic propensity of the tested CRC xenograft tumors. In this study we address to molecular mechanisms of how CD44 knockdown (kd) can result in such substantial changes of tumor properties. Base on the data of miRNA-Seq in combination of bioinformatic analysis the role of miRNA expression changes in the metastasis prevention by CD44 kd was investigated. Among all differentially expressed miRNAs three upregulated miRNAs of Let-7 family (hsa-let-7a-5p, hsa-let-7b-5p, and hsa-let-7c-5p) and two upregulated isoforms of miR-203a (canonical has-miR-203a-3p and its +1 5'-isoform) were revealed as potentially involved in regulation of CD44-mediated metastasis. The results of gene set analysis of differentially expressed mRNA-targets of these miRNAs and analysis of key regulators involved in the determined changes of both mRNA and miRNA expression profiles suggests CD44-STAT3-Let-7 miRNAs axis as one of the most relevant in regulation of colon cancer metastasis by CD44.

ORGANISM(S): Homo sapiens

PROVIDER: GSE284708 | GEO | 2024/12/19

REPOSITORIES: GEO

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