Long non-coding RNA tumor suppressor candidate 7 advances chemotherapy sensitivity of endometrial carcinoma through targeted silencing of miR-23b

Tumour Biol. 2017 Jun;39(6):1010428317707883. doi: 10.1177/1010428317707883.

Abstract

Endometrial carcinoma is the most common malignant tumor of the female genital tract worldwide. TUSC7 (tumor suppressor candidate 7) is an antisense long non-coding RNA and is downregulated and acts as a potential tumor suppressor in several malignant tumors. In this study, the low expression of TUSC7 was confirmed in endometrial carcinoma tissues and was associated with high pathological stages of endometrial carcinoma, which revealed that TUSC7 might be involved in tumorigenesis and progression of endometrial carcinoma. Moreover, the expression of TUSC7 in endometrial carcinoma tissues and cell lines resistant to CDDP and Taxol was lower than that in sensitive endometrial carcinoma tissues and cell lines, which indicated that the TUSC7 expression level was positively correlated with the response of endometrial carcinoma patients to chemotherapy with CDDP and Taxol. TUSC7 upregulation inhibited proliferation, blocked cells at G1 phase, and advanced apoptosis and chemotherapy sensitivity to CDDP and Taxol in HEC1A/CR cell line. Furthermore, miR-23b was upregulated in endometrial carcinoma and negatively correlated with the expression of TUSC7. RNA pull-down assay indicated that TUSC7 could specifically silence the expression of miR-23b in HEC1A/CR cell line; miR-23b was a target gene of TUSC7. MiR-23b upregulation mostly reversed the TUSC7-induced regulatory effects on HEC1A/CR cell line. In summary, long non-coding RNA TUSC7 was underexpressed in endometrial carcinoma, especially in endometrial carcinoma chemotherapy-resistant tissues and cell lines and acted as a potential tumor suppressor gene to inhibit cell growth as well as advance the chemotherapy sensitivity through targeted silencing of miR-23b, which might provide a new therapeutic target to endometrial carcinoma.

Keywords: Endometrial carcinoma; chemotherapy; long non-coding RNA; miciroRNA-23b; tumor suppressor candidate 7.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Long Noncoding / genetics*

Substances

  • MIRN23a microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • loc285194 LncRNA, human