Shanshan Shi1, Tong Wu2, Zechen Ma3, Xiudi Zhang4, Ke Xu4, Qi Tian1, Liming Gao1, Xiaobo Yin1, Shufeng Xu5, Shengbo Yang6. 1. First Hospital of Qinhuangdao, No. 258, Wenhua Road, Haigang District, Qinhuangdao, 066000, Hebei Province, People's Republic of China. 2. Graduate School of Zunyi Medical University, No. 6, Xuefu West Road, Xinpuxin District, Zunyi, 563003, Guizhou Province, People's Republic of China. 3. Medical College, Tianjin University, Tianjin, 300072, People's Republic of China. 4. Graduate School of Hebei Medical University, Shijiazhuang, 050017, People's Republic of China. 5. First Hospital of Qinhuangdao, No. 258, Wenhua Road, Haigang District, Qinhuangdao, 066000, Hebei Province, People's Republic of China. doctorxsf@163.com. 6. Graduate School of Zunyi Medical University, No. 6, Xuefu West Road, Xinpuxin District, Zunyi, 563003, Guizhou Province, People's Republic of China. yangshengbo8205486@163.com.
Abstract
PURPOSE: Serum-derived extracellular vesicles (EVs) have been reported to play an important role in non-small cell lung cancer (NSCLC). The current study sought to explore the effect of serum-EVs delivering m6A methylation regulator heterogeneous nuclear ribonucleoprotein C (HNRNPC) on the development of NSCLC through the regulation of discs large-associated protein 5 (DLGAP5). METHODS: NSCLC-related RNA-Seq and clinical data were first obtained from the TCGA database to screen differentially expressed m6A-related regulators, which were intersected with the differential genes in NSCLC-related microarray GSE43458 obtained from the GEO database for survival analysis and clinical correlation analysis. Correlation between HNRNPC and DLGAP5 expression was evaluated. Serum-EVs were isolated and identified, and the uptake of EVs by A549 cells was visualized using fluorescence microscopy. In vivo xenograft tumor models and tumor metastasis models were constructed in nude mice to observe growth and metastasis of NSCLC cells. RESULTS: HNRNPC was associated with poor prognosis and metastasis of NSCLC, and further implicated in the regulation of DNA replication and cell cycle-related pathways. HNRNPC might promote the growth and metastasis of NSCLC by identifying m6A modification of DLGAP5 mRNA. Serum-EVs delivered HNRNPC to NSCLC cells in vitro. In vivo experimentation further confirmed that serum-EVs could deliver HNRNPC to promote the growth and metastasis of NSCLC cells in nude mice. CONCLUSIONS: Our findings highlight that serum-EVs can deliver HNRNPC to NSCLC cells, wherein HNRNPC recognizes the m6A modification of DLGAP5 mRNA, thus ultimately promoting NSCLC growth and metastasis.
PURPOSE: Serum-derived extracellular vesicles (EVs) have been reported to play an important role in non-small cell lung cancer (NSCLC). The current study sought to explore the effect of serum-EVs delivering m6A methylation regulator heterogeneous nuclear ribonucleoprotein C (HNRNPC) on the development of NSCLC through the regulation of discs large-associated protein 5 (DLGAP5). METHODS: NSCLC-related RNA-Seq and clinical data were first obtained from the TCGA database to screen differentially expressed m6A-related regulators, which were intersected with the differential genes in NSCLC-related microarray GSE43458 obtained from the GEO database for survival analysis and clinical correlation analysis. Correlation between HNRNPC and DLGAP5 expression was evaluated. Serum-EVs were isolated and identified, and the uptake of EVs by A549 cells was visualized using fluorescence microscopy. In vivo xenograft tumor models and tumor metastasis models were constructed in nude mice to observe growth and metastasis of NSCLC cells. RESULTS: HNRNPC was associated with poor prognosis and metastasis of NSCLC, and further implicated in the regulation of DNA replication and cell cycle-related pathways. HNRNPC might promote the growth and metastasis of NSCLC by identifying m6A modification of DLGAP5 mRNA. Serum-EVs delivered HNRNPC to NSCLC cells in vitro. In vivo experimentation further confirmed that serum-EVs could deliver HNRNPC to promote the growth and metastasis of NSCLC cells in nude mice. CONCLUSIONS: Our findings highlight that serum-EVs can deliver HNRNPC to NSCLC cells, wherein HNRNPC recognizes the m6A modification of DLGAP5 mRNA, thus ultimately promoting NSCLC growth and metastasis.
Authors: Antonello Di Paolo; Marzia Del Re; Iacopo Petrini; Giuseppe Altavilla; Romano Danesi Journal: Epigenomics Date: 2016-08-01 Impact factor: 4.778
Authors: Ahmed S K Al-Khafaji; Michael W Marcus; Michael P A Davies; Janet M Risk; Richard J Shaw; John K Field; Triantafillos Liloglou Journal: Oncol Lett Date: 2017-04-07 Impact factor: 2.967