Low expression of long noncoding XLOC_010588 indicates a poor prognosis and promotes proliferation through upregulation of c-Myc in cervical cancer

Gynecol Oncol. 2014 Jun;133(3):616-23. doi: 10.1016/j.ygyno.2014.03.555. Epub 2014 Mar 22.

Abstract

Objective: The identification and investigation of cancer-associated long non-coding RNAs are important for understanding the molecular biology of cancer. The aim of the present study was to examine the expression pattern of lncRNA XLOC_010588 in cervical cancer and to evaluate its biological role and clinical significance in tumor progression.

Methods: We examined the expression of XLOC_010588 in 218 cervical cancer tissues and matched 218 adjacent normal tissues using real-time qRT-PCR. Over-expression and RNA interference approaches were used to investigate the biological functions of XLOC_010588. The effect of XLOC_010588 on proliferation was evaluated by MTT and BrdU assays. Western blot assays were used to investigate the molecular mechanism by which XLOC_010588 increases cervical cancer cell proliferation.

Results: The results showed that XLOC_010588 expression in cervical cancer was significantly downregulated. Decreased XLOC_010588 expression was correlated with FIGO stage, tumor size and SCC-Ag. Moreover, cervical cancer patients with XLOC_010588 lower expression have shown poorer prognosis. Multivariate Cox regression analyses showed that XLOC_010588 expression served as an independent predictor for overall survival. Ectopic expression of XLOC_010588 inhibited the proliferation of HeLa and SiHa cells. By contrast, knockdown of XLOC_010588 promoted the growth of HCC94 cells. Western blot assays confirmed that XLOC_010588 physically associates with c-Myc, consequently decreasing the expression of c-Myc. The expression of XLOC_010588 and c-Myc is strongly correlated in cervical cancer tissues.

Conclusion: These results suggested that XLOC_010588 plays a pivotal role in cervical cancer cell proliferation via decreasing c-Myc expression and implicated the potential application of XLOC_010588 in cervical cancer therapy.

Keywords: Cervical cancer; Long noncoding RNA; XLOC_010588; c-Myc.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / physiology
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • TUSC8 long non-coding RNA, human