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Downregulated miR-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nin one
1Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
Background:
Nin one binding protein (NOB1) was identified as a potential oncogene in human glioma and miR-646 plays an important role in human growth and development. However, the underlying molecular mechanisms of NOB1 in tumorigenicity and its correlation with miR-646 in renal cell carcinoma (RCC) have not been investigated.
Methods:
We performed bioinformatic analysis to explore miRNA targeting NOB1. The expression of NOB1 and miR-646 from 100 cases of clear cell RCC (ccRCC) and 30 cases of adjacent non-tumour tissues were detected by quantitative real-time PCR. The expression of miR-646 was correlated with NOB1 expression, tumour features and patient metastasis-free survival. The effect of overexpression of mir-646 on renal cancer cell proliferation was detected by colony formation in soft agar. Using a xenograft tumour model, we observed the in vivo tumorigenesis effect of miR-646 and NOB1.
Results:
miR-646 negatively regulated NOB1 and inhibited the proliferation and migration of renal cancer cells. There was a significant upregulation of NOB1 in ccRCC and it was further increased in metastatic cases, while miR-646 was downregulated in tumour tissues and further decreased in metastatic ccRCC. Additionally, expression of miR-646 was inversely correlated with the expression of NOB1. The downregulation of miR-646 also indicated a higher probability of developing metastasis. Most importantly, miR-646 expression was an independent predictor of ccRCC metastasis by the univariate analysis and binary logistic regression model (both P<0.05). Colony formation in soft agar and xenograft tumour model suggested that miR-646 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, suppression of NOB1 increased the phosphorylation of several proteins in MAPK pathway.
Conclusions:
Downregulated miR-646 in ccRCC was associated with tumour metastasis through MAPK pathway by targeting NOB1. miR-646 and NOB1 may play an important role in the development of ccRCC.
Insights
MicroRNA-646 (miR-646) downregulation in clear cell renal cell carcinoma (ccRCC) promotes metastasis by targeting Nin one binding protein (NOB1) via the MAPK pathway. Restoring miR-646 may inhibit ccRCC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Nin one binding protein (NOB1) is a potential oncogene in glioma.
- MicroRNA-646 (miR-646) is crucial for growth and development.
- The roles of NOB1 and miR-646 in renal cell carcinoma (RCC) tumorigenesis are unknown.
Purpose of the Study:
- Investigate the molecular mechanisms of NOB1 in RCC.
- Determine the correlation between NOB1 and miR-646 in ccRCC.
- Assess the potential of miR-646 as a therapeutic target.
Main Methods:
- Bioinformatic analysis to identify miRNA targeting NOB1.
- Quantitative real-time PCR to measure NOB1 and miR-646 expression in ccRCC tissues.
- In vitro proliferation assays (colony formation) and in vivo xenograft models.
- Correlation analysis between miR-646, NOB1, tumor features, and patient survival.
Main Results:
- miR-646 negatively regulates NOB1, inhibiting renal cancer cell proliferation and migration.
- NOB1 is upregulated, while miR-646 is downregulated in ccRCC, particularly in metastatic cases.
- miR-646 expression is inversely correlated with NOB1 and predicts a higher risk of metastasis.
- NOB1 suppression affects MAPK pathway signaling.
Conclusions:
- Downregulated miR-646 in ccRCC is linked to metastasis via NOB1 targeting and the MAPK pathway.
- miR-646 and NOB1 are significant players in ccRCC development and progression.
- miR-646 warrants further investigation as a potential biomarker and therapeutic target for ccRCC.
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