c-Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T-cell lymphoma.

Abstract

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor outcomes. The treatment of NKTCL requires intensive chemotherapy. Long noncoding RNAs (lncRNAs) have been implicated in many cancers, including NKTCL. The elucidation of the multidrug resistance (MDR) may greatly contribute to explore novel therapeutic strategies. Herein, we explored the roles and potential regulatory mechanism of lncRNAs small nucleolar RNA host gene 12 (SNHG12) in MDR of NKTCL. We found that SNHG12 was upregulated in NKTCL tissue sections, and its high expression was positively correlated with clinical grade of malignancy of NKTCL. c-Myc and SNHG12 expression was upregulated in NKTCL cell lines. c-Myc- and SNHG12 overexpression promoted proliferation and inhibited sensitivity to cisplatin (CDDP) in NK/T-cell lymphoma cell line YTS cells, and c-Myc and SNHG12-downregulation inhibited proliferation and enhanced sensitivity to CDDP in SNK-6 cells. Moreover, c-Myc- and SNHG12 overexpression increased Ki67 and P-gp expression in YTS cells, whereas c-Myc and SNHG12-downregulation reduced the Ki67 and P-gp expression in SNK-6 cells. Correlational analyses revealed that c-Myc expression was positively correlated with SNHG12 expression in NKTCL tissues. Mechanism research showed that SNHG12 was a direct transcriptional target of c-Myc and c-Myc promoted SNHG12 expression in NKTCL cell lines. Further research showed that SNHG12 overexpression reversed the effects of c-Myc downregulation on proliferation and sensitivity to CDDP in NKTCL cell lines. Taken together, our findings first report that c-Myc mediated upregulation of SNHG12 promotes proliferation and inhibits drug sensitivity in NKTCL, which provides new insights into the therapeutic target for NKTCL.

• Authors: Linan Zhu, Xudong Zhang, Xiaorui Fu, Zhaoming Li, Zhenchang Sun, Jingjing Wu, Xinhua Wang, Feng Wang, Xiangke Li, Songtao Niu, Mengjie Ding, Zhenzhen Yang, Wanqiu Yang, Meifeng Yin, Lei Zhang, Mingzhi Zhang
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 8 Pg. 12628-12637 (08 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30825244 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Proto-Oncogene Proteins c-myc
• RNA, Long Noncoding
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Line
• Cell Proliferation
• Cisplatin (pharmacology, therapeutic use)
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphoma, Extranodal NK-T-Cell (drug therapy, metabolism, physiopathology)
• Proto-Oncogene Proteins c-myc (metabolism)
• RNA, Long Noncoding (genetics, physiology)