PMID- 34633654
OWN - NLM
STAT- MEDLINE
DCOM- 20220204
LR  - 20220218
IS  - 1749-0774 (Electronic)
IS  - 0914-7470 (Print)
IS  - 0914-7470 (Linking)
VI  - 35
IP  - 1
DP  - 2022 Jan
TI  - F-circEA1 regulates cell proliferation and apoptosis through ALK downstream 
      signaling pathway in non-small cell lung cancer.
PG  - 260-270
LID - 10.1007/s13577-021-00628-7 [doi]
AB  - 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.
CI  - (c) 2021. The Author(s).
FAU - Huo, Yinping
AU  - Huo Y
AUID- ORCID: 0000-0001-6937-0964
AD  - Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, 
      No 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, China.
AD  - Department of Respiratory Medicine, Pukou Branch Hospital of Jiangsu Province 
      Hospital, No 166, Jiangpu Street, Pukou District, Nanjing, 211800, China.
FAU - Lv, Tangfeng
AU  - Lv T
AD  - Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, 
      No 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, China.
FAU - Ye, Mingxiang
AU  - Ye M
AD  - Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, 
      No 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, China.
FAU - Zhu, Suhua
AU  - Zhu S
AD  - Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, 
      No 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, China.
FAU - Liu, Jiaxin
AU  - Liu J
AD  - Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, 
      No 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, China.
FAU - Liu, Hongbing
AU  - Liu H
AD  - Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, 
      No 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, China. 
      netlhb@126.com.
FAU - Song, Yong
AU  - Song Y
AD  - Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, 
      No 305, East Zhongshan Road, Xuanwu District, Nanjing, 210002, China. 
      yong_song6310@yahoo.com.
LA  - eng
GR  - Grant Nos. 81572273/National Natural Science Foundation of China/
GR  - No. QNRC2016911/Senior Talent Foundation of Jiangsu University/
GR  - No. YKK16246/Nanjing Medical Science and Technology Development Project/
PT  - Journal Article
DEP - 20211011
PL  - Japan
TA  - Hum Cell
JT  - Human cell
JID - 8912329
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Circular)
RN  - EC 2.7.11.30 (ACVRL1 protein, human)
RN  - EC 2.7.11.30 (Activin Receptors, Type II)
RN  - EC 3.4.21.- (EML4 protein, human)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Activin Receptors, Type II/*genetics/*metabolism
MH  - Apoptosis/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/*pathology
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*genetics
MH  - Gene Expression/genetics
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Humans
MH  - Lung Neoplasms/*genetics/*pathology
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - RNA, Circular/genetics/metabolism/*physiology
MH  - Serine Endopeptidases/genetics/metabolism
MH  - Signal Transduction/*genetics/*physiology
PMC - PMC8732839
OTO - NOTNLM
OT  - Apoptosis
OT  - Circular RNA
OT  - EML4-ALK
OT  - F-circEA1
OT  - NSCLC
COIS- The authors have no conflicts of interest to declare.
EDAT- 2021/10/12 06:00
MHDA- 2022/02/05 06:00
PMCR- 2021/10/11
CRDT- 2021/10/11 12:34
PHST- 2021/05/05 00:00 [received]
PHST- 2021/10/01 00:00 [accepted]
PHST- 2021/10/12 06:00 [pubmed]
PHST- 2022/02/05 06:00 [medline]
PHST- 2021/10/11 12:34 [entrez]
PHST- 2021/10/11 00:00 [pmc-release]
AID - 10.1007/s13577-021-00628-7 [pii]
AID - 628 [pii]
AID - 10.1007/s13577-021-00628-7 [doi]
PST - ppublish
SO  - Hum Cell. 2022 Jan;35(1):260-270. doi: 10.1007/s13577-021-00628-7. Epub 2021 Oct 
      11.