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Published on: March 30, 2019
MicroRNA-143-3p Inhibits Wilms' Tumor Cell Growth By Targeting the Ras/Raf/MEK/ERK Pathway
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.
Insights
MicroRNA-143-3p (miR-143-3p) is downregulated in Wilms' tumor (WT) and inhibits cancer cell proliferation. This microRNA may serve as a prognostic biomarker and therapeutic target for WT.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-143-3p (miR-143-3p) is a known tumor suppressor in various cancers.
- The specific roles and molecular mechanisms of miR-143-3p in Wilms' tumor (WT) progression require further investigation.
Purpose of the Study:
- To determine the expression levels and biological functions of miR-143-3p in Wilms' tumor (WT).
- To elucidate the molecular mechanisms underlying miR-143-3p's role in WT progression.
Main Methods:
- Quantitative-reverse transcription polymerase chain reaction (qRT-PCR) to measure miR-143-3p expression in WT tissues.
- Western blotting to assess protein expression in related signaling pathways.
- Cell line experiments involving miR-143-3p overexpression and k-Ras manipulation.
Main Results:
- miR-143-3p expression was significantly downregulated in WT tissues and correlated with advanced tumor stage and lymph node metastasis.
- Overexpression of miR-143-3p inhibited WT cell proliferation via G0/G1 cell cycle arrest and apoptosis induction.
- k-Ras was identified as a direct target of miR-143-3p; its modulation affected WT cell proliferation, and it reversed miR-143-3p's inhibitory effects.
Conclusions:
- miR-143-3p acts as a tumor suppressor in Wilms' tumor.
- miR-143-3p demonstrates potential as a novel prognostic biomarker and therapeutic target for WT.
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