The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc

Yang, Fan; Wu, Qingjian; Zhang, Le; Xie, Wei; Sun, Xiaoli; Zhang, Yan; Wang, Lei; Dai, Qian; Yu, Hua; Chen, Qian; Sheng, Halei; Qiu, Jing; He, Xiaomei; Miao, Hongming; He, Fengtian; Zhang, Kebin

doi:10.7150/jca.29280

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J Cancer 2019; 10(19):4662-4670. doi:10.7150/jca.29280 This issue Cite

Research Paper

The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc

Fan Yang^1,2,*, Qingjian Wu^3,*, Le Zhang¹, Wei Xie¹, Xiaoli Sun⁴, Yan Zhang², Lei Wang¹, Qian Dai¹, Hua Yu¹, Qian Chen¹, Halei Sheng¹, Jing Qiu¹, Xiaomei He¹, Hongming Miao^2✉, Fengtian He^2✉, Kebin Zhang^1✉

1. Central Laboratory, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China;
2. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing 400038, China;
3. Department of Urology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China.
4. Nursing division, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China.
^*These authors contributed equally to this work.

✉ Corresponding authors: Pro. Kebin Zhang, Central Laboratory, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China. Tel.&Fax: 86-23-68755381, E-mail: zhangkebin12com; Pro. Fengtian He, Depart More

Citation:

Yang F, Wu Q, Zhang L, Xie W, Sun X, Zhang Y, Wang L, Dai Q, Yu H, Chen Q, Sheng H, Qiu J, He X, Miao H, He F, Zhang K. The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc. J Cancer 2019; 10(19):4662-4670. doi:10.7150/jca.29280. https://www.jcancer.org/v10p4662.htm

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Abstract

Background: Long noncoding RNAs (lncRNAs) have been demonstrated to play essential roles in renal cell carcinoma (RCC). However, the role of lncRNA KCNQ1DN in RCC remains unclear.

Methods: The expression of KCNQ1DN in RCC and the corresponding adjacent tissues was measured by qPCR. RNA fluorescence in situ hybridization (FISH) assay, methylation analysis, reporter gene assays and functional tests were performed to reveal the effects of KCNQ1DN on RCC.

Results: In the present study, we found that lncRNA KCNQ1DN was notably decreased in RCC tissues and cell lines. RNA FISH assay showed that KCNQ1DN mainly localized to the cytoplasm. Methylation analysis revealed that the proximal region of KCNQ1DN promoter was hypermethylated in RCC tissues relative to the adjacent normal ones. Functional studies clarified that KCNQ1DN repressed the RCC cell growth and cell cycle progression. Mechanistically, KCNQ1DN inhibited the expression of c-Myc, which might further upregulate cyclin D1 and suppress p27 at mRNA and protein levels in RCC cells. Reporter gene assays revealed that the transcriptional activity of c-Myc promoter was inhibited by KCNQ1DN. The in vivo experiments in nude mice showed that KCNQ1DN overexpression dramatically repressed the growth of xenograft tumors and the expression of corresponding c-Myc.

Conclusion: These results indicated that KCNQ1DN inhibit the growth of RCC cells in vitro and in vivo through repressing the oncogene c-myc, suggesting that KCNQ1DN may serve as a novel target for the treatment of RCC.

Keywords: KCNQ1DN, c-Myc, long non-coding RNA, renal cell carcinoma

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APA

Yang, F., Wu, Q., Zhang, L., Xie, W., Sun, X., Zhang, Y., Wang, L., Dai, Q., Yu, H., Chen, Q., Sheng, H., Qiu, J., He, X., Miao, H., He, F., Zhang, K. (2019). The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc. Journal of Cancer, 10(19), 4662-4670. https://doi.org/10.7150/jca.29280.

ACS

Yang, F.; Wu, Q.; Zhang, L.; Xie, W.; Sun, X.; Zhang, Y.; Wang, L.; Dai, Q.; Yu, H.; Chen, Q.; Sheng, H.; Qiu, J.; He, X.; Miao, H.; He, F.; Zhang, K. The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc. J. Cancer 2019, 10 (19), 4662-4670. DOI: 10.7150/jca.29280.

NLM

CSE

Yang F, Wu Q, Zhang L, Xie W, Sun X, Zhang Y, Wang L, Dai Q, Yu H, Chen Q, Sheng H, Qiu J, He X, Miao H, He F, Zhang K. 2019. The long noncoding RNA KCNQ1DN suppresses the survival of renal cell carcinoma cells through downregulating c-Myc. J Cancer. 10(19):4662-4670.

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