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

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.

• Authors: Yuenan Liu, Gong Cheng, Ziwei Huang, Lin Bao, Jingchong Liu, Cheng Wang, Zhiyong Xiong, Lijie Zhou, Tianbo Xu, Di Liu, Hongmei Yang, Ke Chen, Xiaoping Zhang
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 7 Pg. 515 (07 08 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 32641718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CDCA3 protein, human
• Cell Cycle Proteins
• RNA, Long Noncoding
• RNA, Messenger
• SNHG12 long non-coding RNA, human
• Sp1 Transcription Factor
• Sunitinib

Topics

• Animals
• Carcinoma, Renal Cell (drug therapy, genetics, pathology)
• Cell Cycle Proteins (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Progression
• Drug Resistance, Neoplasm (drug effects, genetics)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Kidney Neoplasms (drug therapy, genetics, pathology)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Multivariate Analysis
• Neoplasm Invasiveness
• Prognosis
• Protein Binding
• Protein Stability
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Sp1 Transcription Factor (metabolism)
• Sunitinib (pharmacology, therapeutic use)
• Survival Analysis
• Transcription, Genetic
• Up-Regulation (drug effects, genetics)