LNMICC Promotes Nodal Metastasis of Cervical Cancer by Reprogramming Fatty Acid Metabolism

Cancer Res. 2018 Feb 15;78(4):877-890. doi: 10.1158/0008-5472.CAN-17-2356. Epub 2017 Dec 11.

Abstract

Cancer spread to lymph nodes predicts poor survival but underlying mechanisms remain little understood. In this study, we show that overexpression of the long noncoding RNA LNMICC associates with lymph node metastasis of primary cervical cancer, where it serves as an independent high-risk factor in patient survival. Functional investigations demonstrated that LNMICC promoted lymph node metastasis by reprogramming fatty acid metabolism, by recruiting the nuclear factor NPM1 to the promoter of the fatty acid binding protein FABP5. We also found that the prometastatic effects of LNMICC were directly targeted and suppressed by miR-190. Our results establish a new mechanism of lymph node metastasis and highlight LNMICC as a candidate prognostic biomarker and therapeutic target in cervical cancer.Significance: These results establish the role of a novel long noncoding RNA in lymph node metastasis, with implications as a candidate prognostic biomarker and therapeutic target in cervical cancer. Cancer Res; 78(4); 877-90. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fatty Acids / metabolism*
  • Female
  • Humans
  • Lymphatic Metastasis
  • Nucleophosmin
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Fatty Acids
  • NPM1 protein, human
  • RNA, Long Noncoding
  • Nucleophosmin