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LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression

Hong-Ying Sui1, Xiu-Ying Cui2, Cai-Xia Shi1

  • 1The Department of Gynecological Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Cancer Science
|March 9, 2023
PubMed

Insights

M2 macrophage exosomes deliver LRRC75A-AS1 to promote cervical cancer. This molecule suppresses miR-429, increasing SIX1 expression and driving tumor growth and metastasis via the STAT3/MMP-9 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cervical cancer remains a significant global health challenge.
  • The role of long non-coding RNAs (lncRNAs) and exosome-mediated intercellular communication in cancer progression is an emerging area of research.
  • M2 macrophages are known to contribute to tumor microenvironment modulation.

Purpose of the Study:

  • To investigate the role of LRRC75A-AS1, transported by M2 macrophage-derived exosomes, in cervical cancer progression.
  • To elucidate the molecular mechanism by which LRRC75A-AS1 influences cervical cancer cell behavior.
  • To determine the therapeutic potential of targeting this pathway.

Main Methods:

  • Analysis of LRRC75A-AS1 expression in M2 macrophage exosomes and its uptake by cervical cancer cells (Hela).
  • In vitro assays assessing cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
  • Molecular analyses including miRNA target prediction and validation (miR-429, SIX1), Western blotting for STAT3/MMP-9, and in vivo tumor formation/metastasis studies in nude mice.

Main Results:

  • LRRC75A-AS1 was highly expressed in M2 macrophage exosomes and promoted Hela cell proliferation, migration, invasion, and EMT.
  • LRRC75A-AS1 suppressed miR-429, which in turn targeted and repressed SIX1 expression.
  • Overexpression of SIX1 or delivery of LRRC75A-AS1-carrying exosomes counteracted the effects of miR-429 mimics, promoting tumor growth and metastasis in vivo.

Conclusions:

  • LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression.
  • The mechanism involves the repression of miR-429, leading to elevated SIX1 expression and activation of the STAT3/MMP-9 signaling pathway.
  • Targeting the exosomal LRRC75A-AS1/miR-429/SIX1 axis presents a potential therapeutic strategy for cervical cancer.
Keywords:
LRRC75A-AS1M2 macrophagesSIX1cervical cancerexosomesmiR-429

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