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Long non-coding RNA UCA1 promotes cisplatin/gemcitabine resistance through CREB modulating miR-196a-5p in bladder

Jingjing Pan1, Xu Li2, Wenjing Wu1

  • 1Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Cancer Letters
|September 5, 2016
PubMed

Insights

Chemoresistance in bladder cancer is a major challenge. This study reveals that Urothelial Cancer Associated 1 (UCA1) long non-coding RNA promotes chemoresistance by activating CREB and miR-196a-5p, suggesting UCA1 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chemoresistance is a primary obstacle in bladder cancer treatment, with underlying molecular mechanisms remaining largely unknown.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their role in modulating cellular responses to chemotherapy.
  • Urothelial Cancer Associated 1 (UCA1), a lncRNA, is upregulated in bladder cancer and linked to tumor progression and drug resistance.

Purpose of the Study:

  • To elucidate the role of Urothelial Cancer Associated 1 (UCA1) in chemoresistance to cisplatin and gemcitabine in bladder cancer.
  • To investigate the molecular pathway through which UCA1 influences chemosensitivity.
  • To assess the potential of UCA1 as a therapeutic target for overcoming chemoresistance in bladder cancer.

Main Methods:

  • Investigated the effect of UCA1 knockdown and overexpression on bladder cancer cell sensitivity to cisplatin and gemcitabine.
  • Analyzed UCA1's impact on cell proliferation and apoptosis.
  • Explored the regulatory relationship between UCA1, CREB, miR-196a-5p, and p27Kip1 using molecular biology techniques.

Main Results:

  • Knockdown of UCA1 reduced chemosensitivity by suppressing proliferation and inducing apoptosis.
  • Overexpression of UCA1 enhanced chemosensitivity in bladder cancer cells.
  • UCA1 was found to activate CREB, leading to miR-196a-5p expression, which in turn targets p27Kip1, thereby inhibiting apoptosis induced by chemotherapy.

Conclusions:

  • A novel UCA1-CREB-miR-196a-5p signaling axis partially explains UCA1's function in cisplatin/gemcitabine resistance.
  • UCA1 plays a significant role in conferring chemoresistance in bladder cancer.
  • UCA1 represents a promising therapeutic target for improving chemotherapy efficacy in bladder cancer patients.
Keywords:
Bladder cancerCREBDrug resistanceUCA1miR-196a-5p

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