Expression of Long Noncoding RNA Urothelial Cancer Associated 1 Promotes Cisplatin Resistance in Cervical Cancer

Cancer Biother Radiopharm. 2017 Apr;32(3):101-110. doi: 10.1089/cbr.2016.2156.

Abstract

Cisplatin resistance is still one of the main reasons for failure of clinical therapy for cervical cancer. But the underlying molecular mechanisms involved in cisplatin resistance of cervical cancer have still remained unclear. Recent studies reported that long noncoding RNAs (lncRNAs) are novel nonprotein-coding transcripts, which might play a key role in cancer biogenesis and prognosis. One of the lncRNAs, urothelial cancer associated 1 (UCA1), has been shown to promote different types of cancer cell proliferation, migration, and invasion. This study showed that overexpression of UCA1 confers cisplatin resistance by promoting cancer cell proliferation and inhibiting apoptosis. In addition, knockdown of UCA1 remarkably decreased cisplatin resistance in cervical cancer cells. Moreover, results also indicated that UCA1 was involved in signaling pathways modulating cell apoptosis and proliferation. UCA1 suppressed apoptosis by downregulating caspase 3 and upregulating CDK2, whereas enhanced cell proliferation by increased level of survivin and decreased level of p21. This study reports for the first time that UCA1 might play an important role in the cisplatin resistance in cervical cancer, and also explain partially how UCA1 promotes cisplatin resistance in cancer cells. These results provide evidence to support that UCA1 can be used as a potential target for a novel therapeutic strategy for cervical cancer.

Keywords: DDP; UCA1; cervical cancer; cisplatin resistance.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Female
  • HeLa Cells
  • Humans
  • Prognosis
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • Signal Transduction
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • RNA, Long Noncoding
  • UCA1 RNA, human
  • Cisplatin