1. Academic Validation
  2. Apelin enhances biological functions in lung cancer A549 cells by downregulating exosomal miR-15a-5p

Apelin enhances biological functions in lung cancer A549 cells by downregulating exosomal miR-15a-5p

  • Carcinogenesis. 2021 Feb 25;42(2):243-253. doi: 10.1093/carcin/bgaa089.
Jingjing Ran 1 2 Yan Li 3 Lei Liu 4 Yihan Zhu 1 Yinyun Ni 5 Hong Huang 1 Zhiqiang Liu 5 Zhiyong Miao 2 Li Zhang 1 5
Affiliations

Affiliations

  • 1 Laboratory of Pathology, Key Laboratory of Transplantation Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  • 2 Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  • 3 Scientific Research Base, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  • 4 Department of Laboratory Medicine, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan Province, China.
  • 5 Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Abstract

Apelin acts as a tumor promoter in multiple malignant tumors; however, its regulatory mechanism remains unclear. Previous studies have indicated that exosomes are pivotal to mediating tumor progression and metastasis. This study examined whether apelin enhances proliferation and invasion ability of lung Cancer cells via exosomal MicroRNA (miRNA). Lung Cancer A549 cells overexpressing apelin and control vector were generated by lentiviral transfection. Exosomes were isolated from the culture supernatant of each cell group and characterized. A-exo and V-exo were, respectively, cocultured with A549 cells, and assays of proliferation, Apoptosis, colony formation and invasion were conducted. Exosomal miRNA Sequencing (miRNA-seq) was performed on A-exo and V-exo to select a candidate miRNA. It was found that A549 cells absorbed more A-exo than V-exo, and A-exo could promote proliferation, colony formation, migration and invasion of A549 cells more than V-exo. Exosomal miRNA-seq data revealed that miR-15a-5p was markedly lower in A-exo compared with V-exo. Low expression of miR-15a-5p was also found in lung Cancer tissues and cell lines, suggesting that miR-15a-5p may have an anti-tumor role. Overexpression of miR-15a-5p in A549 cells was associated with less cell proliferation, migration, invasion and suppressed cell cycle, and lower amounts of CDCA4 (cell division cycle-associated protein 4) indicated that it may be a potential target for miR-15a-5p. This study elucidated a novel regulatory mechanism that apelin may promote proliferation and invasion of lung Cancer cells by inhibiting miR-15a-5p encapsulated in exosomes.

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