Objectives: Colon cancer (CC) is the third largest cancer worldwide. Investigation of the molecular mechanism of CC progression helps to explore novel therapeutic targets. We attempted to understand the modulatory mechanism of miR-142-3p in CC cell autophagy and CC progression, which will lay a theoretical groundwork for seeking potential diagnostic and therapeutic targets for CC. Methods: Through bioinformatics methods, miRNA expression data were subjected to differential analysis for identification of target miRNA. Downstream target mRNAs were predicted, and gene set enrichment analysis was completed. qRT-PCR assessed gene expression in cells. Cell counting kit-8, cell doubling time calculation, colony formation, and flow cytometry were used to assess cellular biological functions. Dual-luciferase assay was used for targeting relationship validation of the target miRNA and mRNA. Western blot was performed to evaluate expression of proteins related to HEDGEHOG signaling pathway and autophagy. Results: miR-142-3p was markedly highly expressed in CC, and high miR-142-3p expression in CC patients was implicated with relatively poor prognosis. Overexpressing miR-142-3p facilitated proliferation and inhibited apoptosis of CC cells, whereas silencing it produced an opposite result. miR-142-3p targeted and decreased TP53INP2 level. TP53INP2 overexpression suppressed the HEDGEHOG signaling pathway and induced the activation of CC cell autophagy. Rescue experiments revealed that influence of the miR-142-3p inhibitor on CC cell proliferation and apoptosis could be reversed by silencing TP53INP2. Conclusion: miR-142-3p hampered tumor cell autophagy and promoted CC progression via targeting TP53INP2, which will offer a fresh research orientation for the diagnosis of CC.

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