LINC02257 regulates colorectal cancer liver metastases through JNK pathway
Xiangan Wu,
Xiaokun Chen,
Xiao Liu,
Bao Jin,
Yuke Zhang,
Yuxin Wang,
Haifeng Xu,
Xueshuai Wan,
Yongchang Zheng,
Lai Xu,
Yi Xiao,
Zhengju Chen,
Haiwen Wang,
Yilei Mao,
Xin Lu,
Xinting Sang,
Lin Zhao,
Shunda Du
Affiliations
Xiangan Wu
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Xiaokun Chen
Department of Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Xiao Liu
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Bao Jin
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Yuke Zhang
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Yuxin Wang
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Haifeng Xu
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Xueshuai Wan
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Yongchang Zheng
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Lai Xu
Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Yi Xiao
Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Zhengju Chen
Pooling Medical Research Institutes, Beijing, China
Haiwen Wang
Pooling Medical Research Institutes, Beijing, China
Yilei Mao
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Xin Lu
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Xinting Sang
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Lin Zhao
Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Corresponding author.
Shunda Du
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Corresponding author.
Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.
