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Updated: Jun 16, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
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.
Background:
Renal cell carcinoma (RCC) is one of the most severe diseases worldwide. More and more studies have found that microRNAs (miRNAs) play very important roles in the occurrence and development of cancer. Previous studies showed that miR-1251-5p is lowly expressed in RCC. However, how miR-1251-5p is involved in regulating the growth and invasion of RCC cells is still unclear. This study aimed to determine the specific effect and molecular mechanism of miR-1251-5p in renal cancer. Our research may provide a new idea for the diagnosis and treatment of RCC.
Methods:
Bioinformatics analyses were performed using starBase, UALCAN, and ONCOLNC databases to evaluate the expression of miR-1251-5p in The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset and its correlation with clinical characteristics of RCC. Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays were utilized to assess the effects of miR-1251-5p on the proliferation and migration of RCC cells. Dual-luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting (WB) analysis were employed to identify and validate the downstream target gene of miR-1251-5p, and functional rescue experiments were conducted to confirm the regulatory relationship between miR-1251-5p and its target gene.
Results:
miR-1251-5p was significantly downregulated in TCGA-KIRC, patient blood samples, and RCC cell lines. Moreover, low miR-1251-5p expression was associated with advanced tumor grade, lymph node metastasis, and worse overall survival in RCC patients. Overexpression of miR-1251-5p effectively inhibited the proliferation and migration of RCC cells. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was identified as a direct downstream target of miR-1251-5p. MTHFD2 was highly expressed in RCC and correlated with poor prognosis. Knockdown of MTHFD2 suppressed RCC cell functions and reversed the tumor-suppressive effect induced by overexpression of miR-1251-5p.
Conclusions:
In the study, miR-1251-5p/MTHFD2 axis is shown to play a vital role in RCC. Therefore, targeting this axis may be a potential therapeutic target combating the progression of RCC.
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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