4.7 Article

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

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CELL DEATH & DISEASE
卷 11, 期 7, 页码 -

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SPRINGERNATURE
DOI: 10.1038/s41419-020-2713-8

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资金

  1. National Key R&D Program of China [2017YFB1303100]
  2. National Natural Science Foundation of China [81672524, 81672528, 81874090]
  3. Hubei Provincial Natural Science Foundation of China [2018CFA038]
  4. Independent Innovation Foundation of Huazhong University of Science and Technology [118530309]
  5. Clinical Research Physician Program of Tongji Medical College, Huazhong University of Science and Technology [5001530015]
  6. Integrated Innovation Team for Major Human Disease Program of Tongji Medical College, Huazhong University of Science and Technology

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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.

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