期刊
HUMAN CELL
卷 35, 期 1, 页码 260-270出版社
SPRINGER JAPAN KK
DOI: 10.1007/s13577-021-00628-7
关键词
Circular RNA; F-circEA1; EML4-ALK; NSCLC; Apoptosis
类别
资金
- National Natural Science Foundation of China Youth Fund [81572273]
- key Young Medical Talents in Jiangsu Province [QNRC2016911]
- Nanjing Medical Science and Technology Development Project [YKK16246]
The study demonstrates that F-circEA1 can regulate cell proliferation and apoptosis in non-small cell lung cancer by affecting the expression of the parental gene EML4-ALK1 and its downstream ALK signaling pathway. Further experiments also show that F-circEA1 has an impact on cell metastasis, invasion, and drug sensitivity.
Studies have confirmed that circular RNA (circRNA) has a stable closed structure, which plays an important role in the progression of tumors. Cancers with positive fusion genes can produce associated fusion circRNA (F-cirRNA). However, there are no reports concerning a role for F-circRNA of the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1 (EML4-ALK1) in non-small cell lung cancer (NSCLC). Our study confirmed the existence of fusion circEA1 (F-circEA1) in NCI-H3122 cells (carrying the EML4-ALK1 gene), F-circEA1 was expressed both in the cytoplasm and nucleus as determined by fluorescence in situ hybridization (FISH) and Sanger sequencing. CCK8 and transwell assays showed that F-circEA1 was beneficial to cell proliferation, metastasis, and invasion. Overexpression of F-circEA1 can also promote cell proliferation, migration and invasion in A549 and SPCA1 cells (non-small cell lung cancer cell line not carrying the EML4-ALK1 gene). Interference with F-circEA1, induced cell cycle arrest and promoted apoptosis as determined by flow cytometry, and increased drug sensitivity to crizotinib in H3122 cells. F-circEA1 directly affected the expression of parental gene EML4-ALK1. Further research found that F-circEA1 can affect the downstream signaling pathway of ALK. In vivo, the growth rate of xenogeneic tumors was reduced and the protein expression level of EML4-ALK1 was significantly decreased in transplanted tumors measured by immunohistochemistry (IHC) after interference with F-circEA1. In conclusion, F-circEA1 can be considered as a proto-oncogene that regulates cell proliferation and apoptosis by affecting the expression of the parental gene EML4-ALK1 and its ALK downstream signaling pathway in non-small cell lung cancer.
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