miR-1251-5p inhibits tumorigenesis and metastasis in renal cell carcinoma by targeting MTHFD2

Yubin Li1, Guanghan Fan2, Gang Wang1

  • 1Department of Urology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.

Abstract

Insights

This study reveals that miR-1251-5p is downregulated in renal cell carcinoma (RCC), inhibiting cancer cell proliferation and migration. Targeting the miR-1251-5p/MTHFD2 axis offers a potential therapeutic strategy for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Renal cell carcinoma (RCC) is a significant global health concern.
  • MicroRNAs (miRNAs) are implicated in cancer development, with miR-1251-5p previously found to be downregulated in RCC.
  • The precise role of miR-1251-5p in RCC growth and invasion remains to be elucidated.

Purpose of the Study:

  • To investigate the specific effects of miR-1251-5p on renal cancer.
  • To elucidate the molecular mechanisms underlying miR-1251-5p's function in RCC.
  • To explore the potential of miR-1251-5p as a diagnostic and therapeutic target for RCC.

Main Methods:

  • Bioinformatic analyses using TCGA-KIRC, starBase, UALCAN, and ONCOLNC databases to assess miR-1251-5p expression and clinical correlations.
  • In vitro assays including CCK-8, colony formation, wound healing, and Transwell assays to evaluate proliferation and migration.
  • Dual-luciferase reporter assay, qRT-PCR, and Western blotting to identify and validate miR-1251-5p targets, with functional rescue experiments.

Main Results:

  • miR-1251-5p was significantly downregulated in RCC tissues, blood samples, and cell lines, correlating with advanced stage, metastasis, and poor survival.
  • Overexpression of miR-1251-5p suppressed RCC cell proliferation and migration.
  • Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was identified as a direct target; its high expression in RCC correlated with poor prognosis, and its knockdown reversed miR-1251-5p's suppressive effects.

Conclusions:

  • The miR-1251-5p/MTHFD2 axis plays a critical role in the progression of renal cell carcinoma.
  • Modulating this axis presents a promising therapeutic avenue for combating RCC.
  • Further research into targeting the miR-1251-5p/MTHFD2 pathway could lead to novel treatments for RCC.

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