Long non-coding RNA CCL14-AS suppresses invasiveness and lymph node metastasis of colorectal cancer cells by regulating MEP1A

Cancer Cell International

Research

Lina Zhu¹  Xin Wang¹  Junfeng Qiu²  Yuanyuan Wu²  Yaxin Zhang³  Yi Zhou³  Xinyan Pan³  Fengtian Li³  Wenting Liao³  Chengmei Huang³  Mingzhou Li⁴  Huali Li⁵  Zhihao Liu⁵ 

[1] Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China;Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China;Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China;Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China;Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China;

关键词: Long noncoding RNA;    AC244100.2;    CCL14-AS;    Colorectal cancer;    Metastasis;    MEP1A;   

DOI  :  10.1186/s12935-023-02866-1

 received in 2022-11-10, accepted in 2023-02-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundLong non-coding RNAs (lncRNAs) play important roles in the biology of colorectal cancer (CRC). There are several lncRNAs associated with invasion and metastasis have been characterized in CRC. However, studies focusing on the precise molecular mechanisms by which lncRNAs function in lymph node (LN) metastasis in CRC are still limited.MethodsIn this study, by analyzing TCGA dataset, we identified that AC244100.2 (termed CCL14-AS), a novel lncRNA enriched in the cytoplasm, was negatively correlated with LN metastasis and unfavorable prognosis of CRC. In situ hybridization was used to examine CCL14-AS expression in clinical CRC tissues. Various functional experiments including migration assay and wound-healing assay were used to investigate the effects of CCL14-AS on CRC cells migration. The nude mice popliteal lymph node metastasis model assay further confirmed the effects of CCL14-AS in vivo.ResultsCCL14-AS expression was significantly downregulated in CRC tissues compared to adjacent normal tissues. In addition, low CCL14-AS expression was correlated with advanced T classification, LN metastasis, distant metastasis, and shorter disease-free survival of CRC patients. Functionally, CCL14-AS overexpression inhibited the invasiveness of CRC cells in vitro and LN metastasis in nude mice. On the contrary, knockdown of CCL14-AS promoted the invasiveness and LN metastasis abilities of CRC cells. Mechanistically, CCL14-AS downregulated the expression of MEP1A via interacting with MEP1A mRNA and reduced its stability. Overexpression of MEP1A rescued the invasiveness and LN metastasis abilities in CCL14-AS-overexpressing CRC cells. Moreover, the expression levels of CCL14-AS was negatively correlated with that of MEP1A in CRC tissues.ConclusionsWe identified a novel lncRNA, CCL14-AS, as a potential tumor suppressor in CRC. Our findings supported a model in which the CCL14-AS/MEP1A axis serves as critical regulator in CRC progression, suggesting a novel biomarker and therapeutic target in advanced CRC.

【 授权许可】

CC BY   
© The Author(s) 2023

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