Long Non-coding RNA SNHG12 Functions as a Competing Endogenous RNA to Regulate MDM4 Expression by Sponging miR-129-5p in Clear Cell Renal Cell Carcinoma

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.

Identification of a Novel Signature and Construction of a Nomogram Predicting Overall Survival in Clear Cell Renal Cell Carcinoma

“…The open access of microarray and high-throughput sequencing data have allowed increasing number of researchers to use comprehensive bioinformatics such as mRNA ( He et al, 2020 ), miRNA ( Xiao et al, 2020 ), and lncRNA ( Wu et al, 2019 ) to explore the novel signatures related to tumor progression and prognosis of ccRCC patients. However, the small sample size of individual studies and differences in sequencing platforms and lab protocols can render great variability among the studies.…”

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

“…Generally speaking, miR-129-5p is considered to be a tumor suppressor and is down-regulated in prostate cancer (PC) 21 , bladder cancer (BC) 22 , etc. Wu Z et al pointed out that the long non-coding RNA SNHG12 acts as a competing endogenous RNA to regulate MDM4 expression by competing with miR-129-5p in ccRCC 12 . In this study, we found that miR-129-5p was signi cantly downregulated in ccRCC by bioinformatics analysis and cell experiments, and it was in agreement with the report of Wu Z et al Besides, overexpression of miR-129-5p was found to suppress ccRCC cell proliferation, migration and invasion by serving as a tumor suppressor.…”

“…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 11 . Despite that the regulatory role of miR-129-5p in ccRCC has been studied before 12 , the regulatory mechanism of miR-129-5p in the occurrence and development of ccRCC requires further exploration.…”

<p>Long Noncoding RNA SNHG12 Indicates the Prognosis and Accelerates Tumorigenesis of Diffuse Large B-Cell Lymphoma Through Sponging microR-195</p>

“…11 The small nucleolar RNA host gene 12 (SNHG12) is located at chromosome 1p35.3 and is involved in multiple cancers, including cervical cancer, renal cell carcinoma, prostate cancer, nasopharyngeal carcinoma, colorectal cancer and hepatocellular carcinoma. [12][13][14][15][16][17] However, SNHG12 biological role and related mechanisms in DLBCL remain unknown.…”