Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells

• Published in: PeerJ (San Francisco, CA) CA), 2017-05, Vol.5, p.e3233-e3233, Article e3233
• Main Authors: Zhu, Ying, Shi, Li-Yun, Lei, Yan-Min, Bao, Yan-Hong, Li, Zhao-Yang, Ding, Fei, Zhu, Gui-Ting, Wang, Qing-Qing, Huang, Chang-Xin
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Biochips; Biology; Cancer stem cell; Cancer treatment; Care and treatment; Cell cycle; Cell growth; Cell proliferation; Cellular signal transduction; Chemotherapy; Cholecystokinin; Comet assay; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Flow cytometry; G1 phase; Genetic aspects; Growth factors; hsa-mir-138-2-3p; Immunology; JNK protein; Kinases; Laryngeal cancer; Lymphoma; MAP kinase; Medical research; MicroRNA; MicroRNAs; miRNA; Oncology; Radiation therapy; Radio-sensitivity; Radiosensitization; Signal pathway; Signal transduction; Stem cells; Teams; Transduction; Translational Medicine; Wnt protein; Yes-associated protein; β-Catenin
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.3233

Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells. To investigate the radiational enhancement of hsa-miR-138-2-3p, we transfected hsa-miR-138-2-3p mimics that were synthesized based on the sequences of hsa-miR-138-2-3p into human laryngeal CSCs (Hep-2, M2e, and TU212 cell lines) to make hsa-miR-138-2-3p overexpressed, and the tumorous specialities of CSCs, like cell proliferation, invasion, apoptosis, cell cycle arrest, and DNA damage were evaluated by CCK-8 assay, clone formation assay, invasion assay, flow cytometry, and comet assay. Furthermore, we explored the signal transduction pathways that regulated the cancer stem cell initiation, development, invasion, apoptosis and cell cycle arrest, which were controlled by hsa-miR-138-2-3p. Overexpressed hsa-miR-138-2-3p played a key role in many anti-cancer biological processes in human laryngeal CSCs: (1) it decreased laryngeal CSCs proliferation and invasion in response to radiotherapy; (2) it increased the proportion of early and late apoptosis in laryngeal CSCs after radiation, raised G1 phase arrest in laryngeal CSCs after radiation, and decreased the proportion of S stage cells of cell cycle that were related to radio-resistance in laryngeal CSCs; (3) it down-regulated the expression of β-catenin in Wnt signal pathway that was related to the tolerance of laryngeal CSCs to radiotherapy; (4) it down-regulated the expression of YAP1 in Hippo signal pathway that regulated cell proliferation, invasion and apoptosis; (5) it up-regulated the expression of p38 and JNK1 in MAPK signal pathway that was concerned to radio-sensitivity. In the present study, it was found that hsa-miR-138-2-3p regulated the Wnt/β-catenin pathways, the Hippo/YAP1 pathways, and the MAPK/p38/JNK1 pathways that were involved in cell proliferation, invasion, apoptosis, cell cycle arrest, radio-resistance and r