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.

Highlights

  • Renal cell carcinoma (RCC) arises from renal tubular epithelial cells, accounting for more than 90% of all renal malignancies [1, 2]

  • We found small nucleolar RNA host gene 12 (SNHG12) could inhibit the carcinogenicity of Clear cell renal cell carcinoma (ccRCC) cells by targeting miR-129-5p and regulate P53 pathway through MDM4

  • We introduced the expression of SNHG12 of ccRCC patients in the International Cancer Genome Consortium (ICGC) database and obtained the same results (Figures 1C,D)

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Summary

Introduction

Renal cell carcinoma (RCC) arises from renal tubular epithelial cells, accounting for more than 90% of all renal malignancies [1, 2]. Most of RCCs occur as clear cell renal cell carcinoma (ccRCC) (75–80%), papillary RCC (10–15%) and chromophobe RCC (5–10%) [2]. Without sensitivity to radiotherapy or chemotherapy, and effective early diagnostic methods, about 20–30% of ccRCC patients demonstrate distant metastasis at the initial diagnosis [5]. It is urgent to find a new effective diagnostic tool or therapeutic target of ccRCC. LncRNAs are transcripts more than 200 nucleotides in length, and most of them do not have the ability to encode proteins [6, 7]. LncRNAs, once considered as the functionless by-products of transcription, have been found

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