miR-129-5p inhibits clear cell renal cell carcinoma cell proliferation, migration and invasion by targeting SPN

Abstract

Objective Our 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. Methods Bioinformatics 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. Results miR-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. Conclusions Our 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.

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

“…Potential downstream miRNAs of RP11-89 were identified using the miRcode database (Table 2 ), which indicated that RP11-89 might play a regulatory role via means of miRNAs. Among these miRNAs, specifically miR-129-5p has been previously reported to exhibit anti-tumor involvement in a variety of cancers [ 26 , 27 ]. In addition, multiple critical regulatory genes of ferroptosis such as ACSL4 and PROM2, are targeted by miR-129-5p according to subsequent intersection analyses.…”

“…Rescue assay proved that the regulatory network is dysregulated in BLCA tumorigenesis. Recent studies have revealed that miR-129-5p plays an anti-tumor effect in a variety of cancers, such as kidney cancer [ 27 , 34 ]. PROM2 plays an important role in the manipulation of ferritin-mediated iron export, which could modify ferroptosis sensitivity of cancer cells.…”

A serum panel of three microRNAs may serve as possible biomarkers for kidney renal clear cell carcinoma

“…Similarly, we found that miR-129-5p was downregulated in KIRC serum than in NCs. Recent research has shown that miR-129-5p has antitumor effects in KIRC [ 28 ]. When SPN is downregulated, miR-129-5p limits KIRC progression [ 28 ].…”

Identification of prognosis-related gene features in low-grade glioma based on ssGSEA

“…SPN can regulate intercellular adhesion, intracellular signaling, cell proliferation, and apoptosis ( 16 ). Gao’s team found that miR-129-5p was beneficial in delaying the malignant progression of clear cell renal carcinoma by targeting the downregulation of SPN ( 17 ). IL18 is a proinflammatory cytokine with important functions, such as induction of angiogenesis and regulation of immune function, and is involved in the progress of many inflammatory diseases, immune disorders, and tumors ( 18 ).…”