Long noncoding RNA LINP1 acts as an oncogene and promotes chemoresistance in breast cancer

Cancer Biol Ther. 2018 Feb 1;19(2):120-131. doi: 10.1080/15384047.2017.1394543. Epub 2018 Jan 2.

Abstract

Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in a number of biological processes; however, further study is still warranted to comprehensively reveal their functions. In this study, we showed that the lncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1) was related to breast cancer cell proliferation, metastasis and chemoresistance. Loss- and gain-of function studies were used to assess the role of LINP1 in promoting breast cancer progression. LINP1 knockdown mitigated breast cancer cell growth by inducing G1-phase cell cycle arrest and apoptosis. LINP1 also promoted breast cancer cell metastasis and influenced the expression of epithelial-mesenchymal transition-related markers. We identified p53 as a regulator of LINP1, and LINP1 overexpression could restore the metastatic effects of p53. Furthermore, LINP1 was upregulated in doxorubicin- and 5-fluorouracil-resistant cells and induced chemoresistance. We also observed that LINP1 enrichment played a critical functional role in chemoresistance by inhibiting chemotherapeutics-induced apoptosis. Moreover, LINP1 in tumors was associated with lower overall survival and disease-free survival. In conclusion, LINP1 may serve as a potential oncogene and chemoresistance-related regulator of breast cancer cells, suggesting that LINP1 might be a potent therapeutic target and might reduce chemoresistance in breast cancer.

Keywords: LINP1; breast cancer; chemoresistance; oncogene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Breast
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Disease Progression
  • Disease-Free Survival
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Oncogenes
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • LINP1 non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Doxorubicin
  • Fluorouracil

Grants and funding

This work was supported by the National Natural Science Foundation of China (No.81272903; No.81672613), the Key Research and Development Program of Shandong Province (No.2016GGE2775), the Shandong Science and Technology Development Plan (2016CYJS01A02) and a Special Support Plan for National High-Level Talents (“Ten Thousand Talents Program”) to Qifeng Yang.