Myc manipulates the miRNA content and biologic functions of small cell lung cancer cell-derived small extracellular

Onur Tokgün1,2, Kubilay İnci3

  • 1Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey. onur_tokgun@hotmail.com.

Abstract

Insights

Small extracellular vesicles (sEVs) from small cell lung cancer (SCLC) cells promote normal lung cell growth and migration. MYC gene expression influences sEV function and miRNA content, suggesting sEVs and MYC as potential SCLC therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • MYC gene amplification/overexpression occurs in 20% of small cell lung cancers (SCLCs).
  • Myc and Myc-dependent pathways are potential therapeutic targets in SCLC.
  • Small extracellular vesicles (sEVs) are implicated in cancer progression, but their association with Myc in SCLC is unexplored.

Purpose of the Study:

  • To investigate the role of Myc in regulating the function and miRNA composition of small extracellular vesicles (sEVs) in small cell lung cancer (SCLC).
  • To determine if SCLC-derived sEVs can modulate the behavior of normal lung cells.

Main Methods:

  • Small extracellular vesicles (sEVs) were isolated from SCLC cell lines (H82 and H209) with manipulated Myc expression.
  • Normal human umbilical vein endothelial cells (HUVECs) and MRC-5 lung fibroblasts were treated with SCLC-derived sEVs.
  • Cellular activity (proliferation, migration) of recipient cells was assessed using cell growth, wound healing, and transwell assays.
  • miRNA profiling of SCLC cells and their derived sEVs was performed using microarray and qRT-PCR.

Main Results:

  • SCLC-derived sEVs significantly increased proliferation and migration of normal lung cells (HUVECs and MRC-5).
  • Myc manipulation in SCLC cells altered the miRNA composition of both the cells and their released sEVs.
  • Myc was found to regulate the expression of specific miRNAs (hsa-miR-7, hsa-miR-9, hsa-miR-125b, hsa-miR-181a_2, hsa-miR-455, hsa-miR-642, hsa-miR-4417) in SCLC cells and their sEVs.

Conclusions:

  • Small extracellular vesicles (sEVs) and MYC are critical targets for SCLC therapeutic strategies.
  • MYC expression levels influence the functional properties and miRNA cargo of sEVs in SCLC.
  • SCLC-derived sEVs possess the capability to alter the behavior of normal lung cells, highlighting their role in tumor progression.

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