Mingjiu Chen1, Zhenkun Xia1, Jie Deng2. 1. Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People's Republic of China. 2. Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, Hunan, 410005, People's Republic of China. chenmingjiu@csu.edu.cn.
Abstract
OBJECTIVE: This study clarified the function of human umbilical cord mesenchymal stem cell (hUCMSC)-derived extracellular vesicle (EV)-enclosed miR-655-3p in esophageal squamous cell carcinoma (ESCC). METHODS: A Chi-square test and the Kaplan-Meier estimator were used to analyze the prognosis of ESCC in relation to the expression of miR-655-3p. ESCC cells were incubated with PBS or hUCMSC-derived EVs (hUCMSC-EVs) in the conditions of gene modification, after which the malignant behaviors of ESCC cells were assessed and the molecular interactions were determined. The effect of hUCMSC-derived EV-miR-655-3p was also investigated in a nude mouse model of ESCC. RESULTS: Low expression of miR-655-3p indicated poor prognosis of ESCC. hUCMSC-EVs suppressed the malignant behaviors of ESCC cells and the growth and liver metastasis of transplanted tumors. Inhibition of miR-655-3p in hUCMSCs impaired the therapeutic effect of hUCMSC-EVs. LMO4, targeted by miR-655-3p, activated the transcription of HIF-1α by sequestering HDAC2 from HIF-1α promoter. Knockdown of LMO4 suppressed ESCC cell activities, while overexpression of HIF-1α counteracted the tumor suppressive effect of LMO4 knockdown. CONCLUSION: miR-655-3p enclosed in hUCMSC-derived EVs inhibits ESCC progression partially by inactivating HIF-1α via the LMO4/HDAC2 axis.
OBJECTIVE: This study clarified the function of human umbilical cord mesenchymal stem cell (hUCMSC)-derived extracellular vesicle (EV)-enclosed miR-655-3p in esophageal squamous cell carcinoma (ESCC). METHODS: A Chi-square test and the Kaplan-Meier estimator were used to analyze the prognosis of ESCC in relation to the expression of miR-655-3p. ESCC cells were incubated with PBS or hUCMSC-derived EVs (hUCMSC-EVs) in the conditions of gene modification, after which the malignant behaviors of ESCC cells were assessed and the molecular interactions were determined. The effect of hUCMSC-derived EV-miR-655-3p was also investigated in a nude mouse model of ESCC. RESULTS: Low expression of miR-655-3p indicated poor prognosis of ESCC. hUCMSC-EVs suppressed the malignant behaviors of ESCC cells and the growth and liver metastasis of transplanted tumors. Inhibition of miR-655-3p in hUCMSCs impaired the therapeutic effect of hUCMSC-EVs. LMO4, targeted by miR-655-3p, activated the transcription of HIF-1α by sequestering HDAC2 from HIF-1α promoter. Knockdown of LMO4 suppressed ESCC cell activities, while overexpression of HIF-1α counteracted the tumor suppressive effect of LMO4 knockdown. CONCLUSION: miR-655-3p enclosed in hUCMSC-derived EVs inhibits ESCC progression partially by inactivating HIF-1α via the LMO4/HDAC2 axis.
Authors: Xiaoyan Cai; Zheng Zhao; Jiangnan Dong; Qiang Lv; Bei Yun; Jiangqi Liu; Yan Shen; Jie Kang; Jun Li Journal: Cell Death Dis Date: 2019-02-22 Impact factor: 8.469