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Long Non-coding RNA SNHG12 Functions as a Competing Endogenous RNA to Regulate MDM4 Expression by Sponging miR-129-5p
Zhipeng Wu1, Dongming Chen1, Kai Wang1
1Department of Urology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC), the most common histological subtype of kidney cancer, shows poor prognosis, and non-sensitivity to radiotherapy or chemotherapy. The lncRNA small nucleolar RNA host gene 12 (SNHG12) has been revealed to play a carcinogenic role in various neoplasms, but the underlying mechanism in ccRCC is still unclear. To explore the potential role of SNHG12 in ccRCC, the data downloaded from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) Data Portal was used to compare the expression of SNHG12 in tumors and adjacent normal tissues. MRNA microarray and quantitative real-time PCR revealed that SNHG12 was overexpressed in the ccRCC tissues and cell lines. Functional inhibition of SNHG12 suppressed the viability and mobility of ccRCC cells. Mechanistically, dual luciferase assay and RNA immunoprecipitation (RIP) assay showed that miR-129-5p could bind to SNHG12 directly. There was a negative relationship between SNHG12 and miR-129-5p. What's more, we used bioinformatics-based prediction software to predict the target genes of miR-129-5p. Through data analysis and experimental verification, we found MDM4, a regulatory factor in p53 pathway, was involved in this ceRNA network. Our findings demonstrated that SNHG12 served as a sponge for miR-129-5p to regulate the expression of MDM4 and p53 pathway in the development of ccRCC.
Insights
Small nucleolar RNA host gene 12 (SNHG12) promotes clear cell renal cell carcinoma (ccRCC) by sponging miR-129-5p, impacting MDM4 and the p53 pathway. This finding offers new insights into ccRCC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype with poor prognosis.
- Current treatments for ccRCC often show limited efficacy.
- The role of long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) in ccRCC pathogenesis is not well understood.
Purpose of the Study:
- To investigate the role of SNHG12 in the development of ccRCC.
- To elucidate the molecular mechanism underlying SNHG12's function in ccRCC.
Main Methods:
- Analysis of TCGA and ICGC databases for SNHG12 expression.
- Quantitative real-time PCR and mRNA microarray in ccRCC tissues and cell lines.
- Functional assays (viability, mobility) following SNHG12 inhibition.
- Dual luciferase and RNA immunoprecipitation (RIP) assays to confirm SNHG12-miR-129-5p interaction.
- Bioinformatic prediction and experimental validation of miR-129-5p target genes (MDM4).
Main Results:
- SNHG12 was significantly overexpressed in ccRCC tissues and cell lines compared to normal controls.
- Inhibition of SNHG12 reduced ccRCC cell viability and mobility.
- SNHG12 directly binds to miR-129-5p, exhibiting a negative correlation.
- MDM4 was identified as a target gene of miR-129-5p within a ceRNA network involving SNHG12.
Conclusions:
- SNHG12 acts as a molecular sponge for miR-129-5p in ccRCC.
- This interaction influences the expression of MDM4 and modulates the p53 signaling pathway.
- SNHG12 plays a crucial role in ccRCC progression and may represent a therapeutic target.
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