JHDM1D-AS1-driven inhibition of miR-940 releases ARTN expression to induce breast carcinogenesis

Yonggang Zuo1, Mingde Ma2, Yuqing Wen2

  • 1Department of Breast and Thyroid Surgery, Huaihe Hospital, Henan University, No.115, Ximen Avenue, Kaifeng, 475000, Henan Province, People's Republic of China. zuoyonggang1@163.com.

Abstract

Insights

The JHDM1D-AS1-miR-940-ARTN ceRNA network drives breast cancer (BC) progression. JHDM1D-AS1 promotes BC by sponging miR-940, which normally suppresses tumors by targeting ARTN.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Competitive endogenous RNA (ceRNA) networks, involving long non-coding RNAs (lncRNAs), microRNAs (miRs), and messenger RNAs (mRNAs), offer insights into cancer mechanisms.
  • Understanding these networks is crucial for deciphering the complexities of carcinogenesis.

Purpose of the Study:

  • To elucidate the mechanistic role of the JHDM1D-AS1-miR-940-ARTN ceRNA network in breast cancer (BC) development.
  • To identify potential therapeutic targets for BC treatment based on this network.

Main Methods:

  • In silico prediction of lncRNA-miRNA-mRNA interactions.
  • Experimental validation using RNA immunoprecipitation, RNA pull-down, and luciferase assays.
  • Functional studies involving lentivirus infection and plasmid transfection to modulate gene expression in BC cells.
  • In vivo assessment of tumorigenic and metastatic abilities.

Main Results:

  • JHDM1D-AS1 was upregulated, while miR-940 was downregulated in BC tissues and cells.
  • JHDM1D-AS1 directly binds to miR-940, promoting BC cell malignancy.
  • ARTN was identified as a direct target of miR-940, with miR-940 exhibiting tumor-suppressive activity via ARTN.
  • In vivo studies confirmed JHDM1D-AS1 promotes BC tumorigenesis and metastasis by upregulating ARTN.

Conclusions:

  • The JHDM1D-AS1-miR-940-ARTN ceRNA network plays a significant role in BC progression.
  • This network represents a promising therapeutic avenue for breast cancer treatment.

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