Exosomal miR-106a-5p derived from intermittently hypoxic non-small-cell lung cancer increases tumor malignancy

• Published in: Physiological reports Vol. 12; no. 15; pp. e16157 - n/a
• Main Authors: Ren, Jie, Jin, Zhuan, Huang, Yongjie
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.08.2024; John Wiley and Sons Inc; Wiley
• Subjects: Angiogenesis; Animals; Apnea; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell culture; Cell growth; Cell Line, Tumor; Cell Proliferation; Cloning; Exosomal miR‐106a‐5p; Exosomes; Exosomes - genetics; Exosomes - metabolism; Gene Expression Regulation, Neoplastic; Humans; Hybridization; Hypoxia; Hypoxia - genetics; Hypoxia - metabolism; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Macrophages; Macrophages - metabolism; Male; Malignancy; Metastases; Metastasis; Mice; Mice, Nude; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Mortality; Non-small cell lung carcinoma; non‐small cell lung cancer; obstructive sleep apnea; Original; Plasmids; Polarization; PTEN; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Reagents; Regular Manuscript; Signal Transduction; Sleep apnea; Sleep Apnea, Obstructive - genetics; Sleep Apnea, Obstructive - metabolism; Sleep disorders; Small cell lung carcinoma; STAT3; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Therapeutic targets; Tumorigenesis; Beijing China; United States > US; China; obstructive sleep apnea; PTEN; Exosomal miR‐106a‐5p; non‐small cell lung cancer; STAT3
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.16157

Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. We explored the possible mechanisms by which OSA may promote the development of non-small cell lung cancer (NSCLC). In this study, NSCLC cells with and without miR-106a-5p inhibition were exposed to IH or room air (RA), and subsequently, exosomes were extracted and identified. Macrophages were incubated with these exosomes to detect the expression of the STAT3 signaling pathway and M2-type macrophage markers, as well as the effect of the macrophages on the malignancy of NSCLC cells. A nude mouse tumorigenesis model was constructed to detect the effects of exosomal miR-106a-5p on M2 macrophage polarization and NSCLC cell malignancy. Our results showed that IH exosomes promoted the polarization of M2 macrophages, thereby promoting the proliferation, invasion, and metastasis of NSCLC cells. Further, Based on microarray analysis of RA and IH exosomes, we discovered that miR-106a-5p, transferred to the macrophages through exosomes, participated in this mechanism by promoting M2 macrophage polarization via down-regulating PTEN and activating the STAT3 signaling pathway in vitro and in vivo. For patients with NSCLC and OSA, exosomal miR-106a-5p levels showed a positive relation to AHI. Exosomal miR-106a-5p represents a potential therapeutic target among patients with concomitant cancer and NSCLC.