机构：[1]Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China[2]Department of Pathology, Huashan Hospital North, Fudan University, Shanghai, China[3]Digestive Endoscopy Center, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]Department of Laboratory Medicine, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China深圳市康宁医院深圳市罗湖区人民医院深圳医学信息中心[5]Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
Long noncoding RNAs (lncRNAs) are involved in the pathology of colorectal cancer (CRC). Current efforts to eradicate CRC predominantly focused on targeting the proliferation of rapidly growing cancer epithelial cells. This is largely ineffective with resistance arising in most tumors after exposure to chemotherapy. Despite the long-standing recognition of the crosstalk between carcinoma-associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment, how CAFs may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that lncRNA CCAL (colorectal cancer-associated lncRNA) promotes oxaliplatin (Oxa) resistance of CRC cells. RNA-ISH shows higher CCAL expressed in the tumor stroma compared to cancer nests of CRC tissues. Functional studies reveal that CCAL is transferred from CAFs to the cancer cells via exosomes, where it suppresses CRC cell apoptosis, confers chemoresistance and activates beta-catenin pathway in vitro and in vivo. Mechanistically, CCAL interacts directly with mRNA stabilizing protein HuR (human antigen R) to increase beta-catenin mRNA and protein levels. Our findings indicate that CCAL expressed by CAFs of the colorectal tumor stroma contributes to tumor chemoresistance and CCAL may serve as a potential therapeutic target for Oxa resistance.
基金：
Program of Shanghai Academic/Technology Research Leader [18XD1400900]; Program for Shanghai Municipal Leading Talent (2015); Innovation Group Project of Shanghai Municipal Health Commission [2019CXJQ03]; National Natural Scienceik Foundation of ChinaNational Natural Science Foundation of China [81672105]; Shanghai Changning District Science and Technology Commission Key Project [CNKW2016Z01]
第一作者机构：[1]Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China[4]Department of Laboratory Medicine, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China[5]Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China[*1]Department of Laboratory Medicine, The Third Affiliated Hospital of Shenzhen University, No. 47 Youyi Road, Shenzhen 518001, China[*2]Department of Gastroenterology, Changhai Hospital, Second Military Medical University, No. 168 Changhai Road, Shanghai 222300, China[*3]Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 middle Urumqi Road, Shanghai 200040, China,
推荐引用方式(GB/T 7714)：
Deng Xuan,Ruan Haoyu,Zhang Xinju,et al.Long noncoding RNA CCAL transferred from fibroblasts by exosomes promotes chemoresistance of colorectal cancer cells[J].INTERNATIONAL JOURNAL OF CANCER.2020,146(6):1700-1716.doi:10.1002/ijc.32608.
APA：
Deng, Xuan,Ruan, Haoyu,Zhang, Xinju,Xu, Xiao,Zhu, Yingfeng...&Guan, Ming.(2020).Long noncoding RNA CCAL transferred from fibroblasts by exosomes promotes chemoresistance of colorectal cancer cells.INTERNATIONAL JOURNAL OF CANCER,146,(6)
MLA：
Deng, Xuan,et al."Long noncoding RNA CCAL transferred from fibroblasts by exosomes promotes chemoresistance of colorectal cancer cells".INTERNATIONAL JOURNAL OF CANCER 146..6(2020):1700-1716
医学