Long noncoding RNA lnc-LEMGC combines with DNA-PKcs to suppress gastric cancer metastasis

• Published in: Cancer letters 2022-01, Vol.524, p.82-90
• Main Authors: Zhang, Hui, Ma, Ran-Ran, Zhang, GuoHao, Dong, Yi, Duan, Miao, Sun, YiYuan, Tian, YaRu, Gao, Ji-Wei, Chen, Xu, Liu, Hai-Ting, Gao, Peng
• Format: Article
• Language: English
• Subjects: Aged; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Deoxyribonucleic acid; DNA; DNA microarrays; DNA-dependent protein kinase; DNA-PKcs; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - genetics; ErbB-1 protein; Female; Focal Adhesion Kinase 1 - genetics; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Humans; lnc-LEMGC; Lymph nodes; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; Molecular modelling; Non-coding RNA; Nucleotides; Phosphorylation; Protein kinase C; Protein-tyrosine kinase; Proteins; RNA, Long Noncoding - genetics; Signal Transduction - genetics; src-Family Kinases - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.09.042

Long non-coding RNAs (lncRNAs) play important roles in cancer development and progression; however, their contributions to gastric cancer metastasis remain largely unknown. By lncRNA microarray screening, our study showed that 453 lncRNAs are dysregulated in gastric cancer tissues with or without lymph node metastasis, of which lnc-LEMGC ranks as one of the most significantly downregulated lncRNAs. Lnc-LEMGC inhibited cell migration and invasion both in vitro and in vivo, by combining with protein DNA-PKcs. Importantly, nucleotides 1300–1800 of lnc-LEMGC prevented DNA-PKcs phosphorylation of serine 2056 and partially abrogated the effects of downstream effectors, ErbB1, SRC and protein tyrosine kinase 2 (FAK), in the epidermal growth factor receptor (EGFR) pathway. The results of this study extend our knowledge of lncRNA's molecular mechanisms, in which lnc-LEMGC functions by directly suppressing the phosphorylation of its combined protein DNA-PKcs and inactivating the DNA-PKcs downstream EGFR signaling. •WHAT IS CURRENT KNOWLEDGE.●Lymph node metastasis and distant metastasis is the chief cause of cancer-related death.●LncRNAs can apply diverse modes of action to regulate cancer processes.●EGFR pathway is one of most frequently activated signaling pathway in gastric cancer.2.WHAT IS NEW HERE●Differential expression lncRNA profiles in gastric cancer samples with or without metastases.●Lnc-LEMGC is down-regulated in metastatic gastric cancer tissues, compared to tissues without metastases.●A direct experimental evidence for the anti-oncogene role of lnc-LEMGC in vitro and in vivo.●Lnc-LEMGC functions by directly suppressing the phosphorylation of its combined protein DNA-PKcs and inactivating the DNA-PKcs downstream EGFR signaling.