Abstract
ObjectiveOur study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC.MethodsBioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities. Flow cytometry was implemented to assess cell cycle and apoptosis.ResultsmiR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities while induced cell cycle arrest in G0/G1 phase and promoted cell apoptosis. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Moreover, overexpressed miR-129-5p remarkably reduced SPN expression in cancer cells, weakened the promoting effect of SPN on cell proliferation, migration, invasion and cell cycle progress, and led to enhanced cell apoptotic activity.ConclusionsOur study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.
Highlights
Renal cell carcinoma (RCC), accounting for 3 % of all adult cancers, is the most common malignancy in adult and one of the leading causes of cancer-related deaths worldwide, with a mortality rate of over 40 % [1]
A research suggests that the dysregulation of miRNAs is associated with the biological characteristics of clear cell renal cell carcinoma (ccRCC), and it may serve as a novel potential biomarker for prognosis and treatment [7]. miR-129-5p is a key tumor regulatory factor that plays an important role in the progression of cancers
TCGA data showed that miR-129-5p was prominently down-regulated in ccRCC tissue (Fig. 1b). qRT-PCR was employed to evaluate miR-129-5p expression in ccRCC cells and normal cells, finding that miR-129-5p was potently down-regulated in ccRCC cell lines (Fig. 1c)
Summary
Renal cell carcinoma (RCC), accounting for 3 % of all adult cancers, is the most common malignancy in adult and one of the leading causes of cancer-related deaths worldwide, with a mortality rate of over 40 % [1]. Gao et al Cancer Cell Int (2021) 21:263 that regulate the metastatic and invasive abilities of ccRCC and study the potential mechanisms underlying ccRCC, so as to develop a novel therapeutic method. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that are emerging as a novel tool for regulating gene expression. A study has indicated that miRNAs are involved in regulating various biological events, such as cell proliferation, differentiation and apoptosis [5]. Numerous studies have elucidated that miR-129-5p is considerably differentially expressed and exerts an essential role in colon cancer [8], liver cancer [9], pancreatic cancer [10 and gastric cancer, etc. Despite that the regulatory role of miR-129-5p in ccRCC has been studied before [12], the regulatory mechanism of miR129-5p in the occurrence and development of ccRCC requires further exploration
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