Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma

Yuenan Liu,Cheng Wang,Tianbo Xu,Gong Cheng,Hongmei Yang,Zhiyong Xiong,Jingchong Liu,Xiaoping Zhang,Ke Chen,Di Liu,Ziwei Huang,Lijie Zhou,Lin Bao

doi:10.1038/s41419-020-2713-8

Yuenan Liu, Cheng Wang + Show 11 more

Open Access

https://doi.org/10.1038/s41419-020-2713-8

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Abstract

Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system and targeted drug resistance is quite common in RCC. Long noncoding RNA SNHG12 (lncRNA SNHG12) has emerged as a key molecule in numerous human cancers, but its functions in renal cell carcinoma (RCC) sunitinib resistance remain unclear. In this study, we found SNHG12 was highly expressed in RCC tissues and in sunitinib-resistant RCC cells and was associated with a poor clinical prognosis. SNHG12 promoted RCC proliferation, migration, invasion and sunitinib resistance via CDCA3 in vitro. Mechanically, SNHG12 bound to SP1 and prevented the ubiquitylation-dependent proteolysis of SP1. Stabilised SP1 bound to a specific region in the promoter of CDCA3 and increased CDCA3 expression. Furthermore, in vivo experiments showed that SNHG12 increased tumour growth and that knocking down SNHG12 could reverse RCC sunitinib resistance. Our study revealed that the lncRNA SNHG12/SP1/CDCA3 axis promoted RCC progression and sunitinib resistance, which could provide a new therapeutic target for sunitinib-resistant RCC.

Highlights

Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system[1]
Small nucleolar RNA host gene 12 (SNHG12) was overexpressed and indicated a poor clinical prognosis in RCC Accumulating studies have demonstrated that Long noncoding RNAs (lncRNAs) play important roles in tumour progression and drug resistance
We studied the differential expression of lncRNAs between tumour and normal tissues from the The Cancer Genome Atlas database (TCGA)-KIRC database

Summary

Introduction

Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system[1]. Among the various pathological types of RCC, ~70–80% are clear cell renal cell carcinoma (ccRCC)[2]. For ~30% of RCC patients, cancer has RCC patients, drug resistance develops within 6–15 months, and the overall survival remains unsatisfactory[5,6,7]. It is necessary to elucidate the potential mechanisms underlying RCC progression and drug resistance. Long noncoding RNAs (lncRNAs) are defined as a group of RNAs with a minimum length of 200 nucleotides that do not encode proteins[8]. Studies have demonstrated their significant roles in the regulation of transcription and translation of protein-coding genes[9,10,11]

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