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Lnc00892 competes with c-Jun to block NCL transcription, reducing the stability of RhoA/RhoC mRNA and impairing bladder cancer invasion

Oncogene volume 40, pages 6579–6589 (2021)Cite this article

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Abstract

Metastasis of bladder cancer is a complex process and has been associated with poor clinical outcomes. However, the mechanisms of bladder cancer metastasis remain largely unknown. The present study found that the long noncoding RNA lnc00892 was significantly downregulated in bladder cancer tissues, with low lnc00892 expression associated with poor prognosis of bladder cancer patients. Lnc00892 significantly inhibited the migration, invasion, and metastasis of bladder cancer cells in vitro and in vivo. In-depth analysis showed that RhoA/C acted downstream of lnc00892 to inhibit bladder cancer metastasis. Mechanistically, lnc00892 reduces nucleolin gene transcription by competitively binding the promoter of nucleolin with c-Jun, thereby inhibiting nucleolin-mediated stabilization of RhoA/RhoC mRNA. Taken together, these findings provide novel insights into understanding the mechanisms of bladder cancer metastasis and suggest that lnc00892 can serve as a potential therapeutic target in patients with invasive bladder cancer.

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Fig. 1: Expression of lnc00892 is significantly lower in the bladder cancer than in the normal bladder tissues and is closely related to the patient’s survival rate.
Fig. 2: Lnc00892 inhibition of bladder cancer cell invasion in vitro and in vivo.
Fig. 3: RhoA and RhoC function downstream of lnc00892 as effectors of BC metastasis.
Fig. 4: Lnc00892 downregulates RhoA and RhoC expression by reducing the stability of their mRNAs in human BC cells.
Fig. 5: Effect of lnc00892 on NCL-mediated regulation of the stability of RhoA and RhoC mRNAs.
Fig. 6: The site of the NCL promoter (−1161 to −895 bp) is involved in the function of lnc00892.
Fig. 7: Specific sites on lnc00892 compete with c-Jun for binding to NCL.

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Acknowledgements

This work was partially supported by the Natural Science Foundation of China NSFC81702530, and Wenzhou Science and Technology Bureau (Y20190065), Key Discipline of Zhejiang Province in Medical Technology (First Class, Category A).

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  1. These authors contributed equally: Shuwei Ren, Ning Zhang, Liping Shen.

Authors and Affiliations

  1. Zhejiang Province Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Shuwei Ren, Ning Zhang, Liping Shen, Yixin Chang, Zhenni Lin, Ning Sun, Yuanmei Zhang, Jiheng Xu, Haishan Huang & Honglei Jin

  2. Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Shuwei Ren

  3. Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Yongyong Lu

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Contributions

HLJ and SWR conceived and designed the project. SWR, NZ, LPS, YXC, ZNL, and NS performed experiments and conducted the statistical analysis; YYL collected the clinical samples; SWR and YMZ performed the animal studies and constructed the plasmids; SWR, NZ, and JHX contributed the bioinformatic analysis; HLJ, SWR, and NZ prepared, wrote the manuscript. HLJ, HSH, and NZ revised the paper. All authors read, discussed the results, and approved the final version of the paper.

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Correspondence to Honglei Jin.

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This study was approved by the ethics committee of Wenzhou Medical University. All the animal experiments performed in the present study were approved by the regulation of the experimental animal ethics committee of Wenzhou Medical University.

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Ren, S., Zhang, N., Shen, L. et al. Lnc00892 competes with c-Jun to block NCL transcription, reducing the stability of RhoA/RhoC mRNA and impairing bladder cancer invasion. Oncogene 40, 6579–6589 (2021). https://doi.org/10.1038/s41388-021-02033-8

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