4.8 Article

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

Journal

ONCOGENE
Volume 40, Issue 48, Pages 6579-6589

Publisher

SPRINGERNATURE
DOI: 10.1038/s41388-021-02033-8

Keywords

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Funding

  1. Natural Science Foundation of China [NSFC81702530]
  2. Wenzhou Science and Technology Bureau [Y20190065]
  3. Key Discipline of Zhejiang Province in Medical Technology

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The study found that the long noncoding RNA lnc00892 is significantly downregulated in bladder cancer tissues and its low expression is associated with poor prognosis. Lnc00892 was shown to inhibit migration, invasion, and metastasis of bladder cancer cells by reducing nucleolin gene transcription and inhibiting nucleolin-mediated stabilization of RhoA/RhoC mRNA. These findings suggest that lnc00892 may serve as a potential therapeutic target for invasive bladder cancer patients.
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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