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Melatonin inhibits triple-negative breast cancer progression through the Lnc049808-FUNDC1 pathway

Anli Yang1, Fu Peng2,3, Lewei Zhu4

  • 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.

Cell Death & Disease
|July 17, 2021
PubMed

Insights

Melatonin suppresses triple-negative breast cancer (TNBC) by downregulating FUNDC1 and lnc049808. This pathway, involving miR-101, offers potential therapeutic strategies for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Melatonin exhibits tumor-suppressive properties through various molecular pathways.
  • Long non-coding RNAs (lncRNAs) are implicated in cancer development, but their interaction with melatonin in triple-negative breast cancer (TNBC) remains unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of melatonin's effect on lncRNAs and messenger RNAs (mRNAs) in TNBC.
  • To identify differentially expressed genes and explore their interaction networks following melatonin treatment in TNBC cell lines.

Main Methods:

  • Microarray analysis to identify differentially expressed mRNAs and lncRNAs in melatonin-treated TNBC cells.
  • In vitro assays (CCK-8, Transwell, colony formation, luciferase reporter, RNA immunoprecipitation) and mouse xenograft models to validate findings.
  • Analysis of the competing endogenous RNA (ceRNA) network involving lncRNAs, mRNAs, and microRNAs.

Main Results:

  • Melatonin treatment downregulated FUNDC1 and lnc049808 in TNBC cell lines.
  • Knockdown of FUNDC1 and lnc049808 significantly inhibited TNBC cell proliferation, invasion, and metastasis.
  • lnc049808 and FUNDC1 function as competing endogenous RNAs (ceRNAs) by binding to miR-101, regulating the pathway.

Conclusions:

  • Melatonin inhibits TNBC progression via the lnc049808-FUNDC1 pathway, mediated by miR-101.
  • Melatonin demonstrates potential as a therapeutic agent for treating triple-negative breast cancer.

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