Tao Wang1, Xiaoxu Wang1, Qianyu Du1, Nan Wu1, Xincheng Liu1, Yuqing Chen2, Xiaojing Wang3. 1. Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui Province, China. 2. Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui Province, China. Electronic address: bbmccyq@126.com. 3. Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui Province, China. Electronic address: wangxiaojing8888@163.com.
Abstract
BACKGROUND: Non-small cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we report on the role of circP4HB in NSCLC. METHODS: First, we evaluated circP4HB levels in patient-derived NSCLC tissue versus paired healthy samples. Next, we conducted experiments in vitro in NSCLC cell-lines and in vivo in a murine xenograft NSCLC model to assess the impact of circP4HB on epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo. The downstream impact of circP4HB on the microRNA miR-133a-5p, and its target the EMT marker vimentin, were also evaluated. RESULTS: NSCLC tumor specimens exhibited higher circP4HB levels in comparison to paired healthy lung samples and was associated with metastatic disease and poorer survival. circP4HB promoted EMT and vimentin expression in vitro and xenograft metastasis in vivo through sequestration of miR-133a-5p. CONCLUSION: circP4HB enhances EMT and metastatic disease through miR-133a-5p sequestration, leading to upregulation of vimentin. Therefore, these findings advocate targeting the circP4HB/miR-133a-5p/vimentin axis as a potential therapeutic option for NSCLC patients.
BACKGROUND:Non-small cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we report on the role of circP4HB in NSCLC. METHODS: First, we evaluated circP4HB levels in patient-derived NSCLC tissue versus paired healthy samples. Next, we conducted experiments in vitro in NSCLC cell-lines and in vivo in a murine xenograft NSCLC model to assess the impact of circP4HB on epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo. The downstream impact of circP4HB on the microRNA miR-133a-5p, and its target the EMT marker vimentin, were also evaluated. RESULTS:NSCLC tumor specimens exhibited higher circP4HB levels in comparison to paired healthy lung samples and was associated with metastatic disease and poorer survival. circP4HB promoted EMT and vimentin expression in vitro and xenograft metastasis in vivo through sequestration of miR-133a-5p. CONCLUSION:circP4HB enhances EMT and metastatic disease through miR-133a-5p sequestration, leading to upregulation of vimentin. Therefore, these findings advocate targeting the circP4HB/miR-133a-5p/vimentin axis as a potential therapeutic option for NSCLCpatients.