Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

LncRNA KCNQ1OT1 facilitates the progression of bladder cancer by targeting MiR-218-5p/HS3ST3B1

Abstract

Long non-coding RNA (lncRNA) is characterized by biological function in diverse cancers. LncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) is well acknowledged to regulate various cancers, while its role in bladder cancer remains unclear. In the present study, we aimed at probing into the impact and detailed mechanisms of KCNQ1OT1 in bladder cancer progression. In this study, we demonstrated that KCNQ1OT1 expression in bladder cancer tissues was notably up-regulated compared with in normal adjacent tissues, and KCNQ1OT1 modulated the malignant phenotypes of bladder cancer cells. Moreover, it was validated that KCNQ1OT1 could specifically bind to miR-218-5p and reduce its expression. Overexpressed miR-218-5p would inhibit the proliferation and metastasis of bladder cancer cells while facilitating apoptosis. In terms of Mechanism, Heparan Sulfate-Glucosamine 3-Sulfotransferase 3B1 (HS3ST3B1) was validated as a target gene of miR-218-5p, and could be regulated by KCNQ1OT1 indirectly. In conclusion, KCNQ1OT1 can promote the progression of bladder cancer through regulation of miR-218-5p/HS3ST3B1, which is expected to serve as a new therapeutic target for bladder cancer.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: The expressions of KCNQ1OT1 in bladder cancer tissues and cell lines were detected by qRT-PCR.
Fig. 2: The impact of overexpression and knockdown of KCNQ1OT1 on proliferation, migration, invasion and apoptosis of SW780 and T24 cell lines, respectively.
Fig. 3: The expressions of KCNQ1OT1 and miR-218-5p and their interaction in bladder cancer tissues and cells.
Fig. 4: The impact of overexpression and inhibition of miR-218-5p on proliferation, migration, invasion, and apoptosis of T24 and SW780 cell lines, respectively.
Fig. 5: The effects of KCNQ1OT1/miR-218-5p on proliferation, migration, invasion, and apoptosis of bladder cancer cells.
Fig. 6: The expressions of miR-218-5p and HS3ST3B1 and their interaction in bladder cancer tissues and cells.

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Mahdavifar N, Ghoncheh M, Pakzad R, Momenimovahed Z, Salehiniya H. Epidemiology, incidence and mortality of bladder cancer and their relationship with the development index in the world. Asian Pac J Cancer Prev. 2016;17:381–6.

    Article  Google Scholar 

  2. Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017;71:96–108.

    Article  Google Scholar 

  3. Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152:1298–307.

    Article  Google Scholar 

  4. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:0–641.

    Article  CAS  Google Scholar 

  5. Parsons C, Adams BD. Targeting noncoding RNAs in disease. J Clin Investig. 2017;127:761–71.

    Article  Google Scholar 

  6. Maria S, Thomas B, Karl P, George C, Martin P. Current insights into long non-coding RNAs (LncRNAs) in prostate cancer. Int J Mol Sci. 2017;18:473.

    Article  Google Scholar 

  7. Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–61.

    Article  CAS  Google Scholar 

  8. Zhang K, Yan J, Yi B, Rui Y, Hu H. High KCNQ1OT1 expression might independently predict shorter survival of colon adenocarcinoma. Future Oncol. 2019;15(Apr):1085–95.

    Article  CAS  Google Scholar 

  9. Sayed D, Abdellatif M. MicroRNAs in development and disease. Physiol Rev. 2011;91:827–87.

    Article  CAS  Google Scholar 

  10. Cui X, Zhou D, Du Q, Wan P, Dong K, Hou H, et al. MicroRNA200a enhances antitumor effects in combination with doxorubicin in hepatocellular carcinoma. Transl Oncol. 2020;13:100805.

    Article  Google Scholar 

  11. Tuo Hang, Wang Yufeng, Wang Liang, Yao Bowen, Li Qing, Wang Cong, et al. MiR-324-3p promotes tumor growth through targeting DACT1 and activation of Wnt/β-catenin pathway in hepatocellular carcinoma. Oncotarget. 2017;8:65687–98.

    Article  Google Scholar 

  12. Zhu Kegan, Ding Hanying, Wang Wengong, Liao Zhicong, Fu Zheng, Hong Yeting, et al. Tumor-suppressive miR-218-5p inhibits cancer cell proliferation and migration via EGFR in non-small cell lung cancer. Oncotarget. 2016;7:28075–85.

    Article  Google Scholar 

  13. AB, McMartin KE, Palese M, Tephly TR. Formate assay in body fluids: application in methanol poisoning. Biochem Med. 1975;13:117–26.

    Article  Google Scholar 

  14. Esko JD, Selleck SB. ORDER OUT OF CHAOS: assembly of ligand binding sites in heparan sulfate1. Annu Rev Biochem. 2002;71:435–71.

    Article  CAS  Google Scholar 

  15. Li Y, Shi B, Dong F, Zhu X, Liu B, Liu Y. Long non-coding RNA DLEU1 promotes cell proliferation, invasion, and confers cisplatin resistance in bladder cancer by regulating the miR-99b/HS3ST3B1 axis. Front Genet. 2019;10:280.

    Article  CAS  Google Scholar 

  16. Zhao HL, Xu SQ, Li Q, Zhao YB, Li X, Yang MP. Long noncoding RNA MIAT promotes the growth and metastasis of non-small cell lung cancer by upregulating TDP43. Eur Rev Med Pharm Sci. 2019;23:3383–9.

    Google Scholar 

  17. Zhao J, Liu HR. Down-regulation of long noncoding RNA DLX6-AS1 defines good prognosis and inhibits proliferation and metastasis in human epithelial ovarian cancer cells via Notch signaling pathway. Eur Rev Med Pharm Sci. 2019;23:3243–52.

    CAS  Google Scholar 

  18. Zhao X, Wang D, Ding Y, Zhou J, Liu G, Ji Z. lncRNA ZEB1-AS1 promotes migration and metastasis of bladder cancer cells by post-transcriptional activation of ZEB1. Int J Mol Med. 2019;44:196–206.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Chen Z, Chen X, Xie R, Huang M, Dong W, Han J, et al. DANCR promotes metastasis and proliferation in bladder cancer cells by enhancing IL-11-STAT3 signaling and CCND1 expression. Mol Ther. 2019;27:326–41.

    Article  CAS  Google Scholar 

  20. Li P, Zhang X, Wang L, Du L, Yang Y, Liu T, et al. lncRNA HOTAIR contributes to 5FU resistance through suppressing miR-218 and activating NF-κB/TS signaling in colorectal cancer. Mol Ther Nucleic Acids. 2017;8:356–69.

    Article  CAS  Google Scholar 

  21. Jiang F, Qi W, Wang Y, Wang W, Fan L. lncRNA PEG10 promotes cell survival, invasion and migration by sponging miR-134 in human bladder cancer. Biomed Pharmacother. 2019;114:108814.

    Article  CAS  Google Scholar 

  22. Miao L, Liu HY, Zhou C, He X, et al. LINC00612 enhances the proliferation and invasion ability of bladder cancer cells as ceRNA by sponging miR-590 to elevate expression of PHF14. J Exp Clin Cancer Res. 2019;38:143.

    Article  Google Scholar 

  23. Gong Wei, Zheng Jian, Liu Xiaobai, et al. Knockdown of long non-coding RNA KCNQ1OT1 restrained glioma cells’ malignancy by activating miR-370/CCNE2 axis. Front Cell Neurosci. 2017;11:84.

    Article  Google Scholar 

  24. Zhang Z, Liu X, Chen J, Su H, Luo Q, Ye J, et al. Heparin sulphate D-glucosaminyl 3-O-sulfotransferase 3B1 plays a role in HBV replication. Virology. 2010;406:280–5.

    Article  CAS  Google Scholar 

  25. Zhang L, Song K, Zhou L, Xie Z, Zhou P, Zhao Y, et al. Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1 (HS3ST3B1) promotes angiogenesis and proliferation by induction of VEGF in acute myeloid leukemia cells. J Cell Biochem. 2015;116:1101–12.

    Article  CAS  Google Scholar 

  26. Zhang Z, Jiang H, Wang Y, Shi M. Heparan sulfate D-glucosamine 3-O-sulfotransferase 3B1 is a novel regulator of transforming growth factor-beta-mediated epithelial-to-mesenchymal transition and regulated by miR-218 in nonsmall cell lung cancer. J Cancer Res Ther. 2018;14:24–29.

    Article  CAS  Google Scholar 

Download references

Funding

Funded by the Educational Department of Liaoning Province L2015576.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yili Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Our study was approved by the ethics review board of the Fourth Affiliated Hospital of China Medical University.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Shi, B., Dong, F. et al. LncRNA KCNQ1OT1 facilitates the progression of bladder cancer by targeting MiR-218-5p/HS3ST3B1. Cancer Gene Ther 28, 212–220 (2021). https://doi.org/10.1038/s41417-020-00211-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-020-00211-6

This article is cited by

Search

Quick links