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. 2023 Mar;29(2):140-147.

MicroRNA-143-3p Inhibits Wilms' Tumor Cell Growth By Targeting the Ras/Raf/MEK/ERK Pathway

  • PMID: 36455140
Free article

MicroRNA-143-3p Inhibits Wilms' Tumor Cell Growth By Targeting the Ras/Raf/MEK/ERK Pathway

Lianhai Zhang et al. Altern Ther Health Med. 2023 Mar.
Free article

Abstract

Background: A previous study found that microRNA-143-3p (miR-143-3p) is a tumor suppressor in various types of human cancer. However, the roles and molecular mechanisms of miR-143-3p in the progression of Wilms' tumor (WT) remain to be clarified. The aim of the present study was to determine the expression and biological functions of miR-143-3p in WT.

Material and methods: The expression levels of miR-143-3p in primary WT tissues and adjacent tissues were determined using quantitative-reverse transcription polymerase chain reaction (qRT-PCR), and the association of the miR-143-3p expression level with various clinicopathological features of WT was investigated. Western blotting was used to evaluate the protein expression of the related signaling pathway.

Results: The expression of miR-143-3p was significantly downregulated in WT tissues and its expression levels were closely associated with tumor stage and lymph node metastasis. Overexpression of miR-143-3p in SK-NEP-1 and G401 cell lines inhibited cell proliferation by G0/G1 cell cycle phase arrest and induction of apoptosis. Moreover, k-Ras, a unique oncogene, was confirmed as a direct target of miR-143-3p, and k-Ras messenger RNA (mRNA) expression was increased in WT tissues and inversely correlated with miR-143-3p. Knockdown of k-Ras by si-k-Ras could inhibit, whereas overexpression of k-Ras could promote. cell proliferation in WT cells. Meanwhile, overexpression of k-Ras reversed the inhibitory effects on WT cells induced by miR-143-3p mimics.

Conclusion: Our findings indicate that miR-143-3p may be a potential novel prognostic biomarker and therapeutic target for WT.

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