PMID- 37884580
OWN - NLM
STAT- MEDLINE
DCOM- 20240102
LR  - 20240313
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Linking)
VI  - 30
IP  - 12
DP  - 2023 Dec
TI  - LncRNA CALML3-AS1 modulated by m(6)A modification induces BTNL9 methylation to 
      drive non-small-cell lung cancer progression.
PG  - 1649-1662
LID - 10.1038/s41417-023-00670-7 [doi]
AB  - Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The 
      carcinogenic roles of lncRNA CALML3 antisense RNA 1 (CALML3-AS1) have been 
      documented. However, the function and potential mechanisms of CALML3-AS1 in the 
      progression of NSCLC need to be further explored. The molecule expression was 
      assessed by qRT-PCR and Western blot. The subcellular localization of CALML3-AS1 
      was observed by fluorescence in situ hybridization (FISH). The malignant 
      behaviors of NSCLC cells were evaluated by CCK-8, colony formation, EdU, wound 
      healing and transwell assays. In vivo xenograft tumor and liver metastatic models 
      were established. The molecular mechanisms were investigated by RIP, RNA 
      pull-down and ChIP assays. The methylation level was detected by MSP. Herein, we 
      found that CALML3-AS1 was upregulated, while butyrophilin-like 9 (BTNL9) was 
      downregulated in NSCLC. Functionally, CALML3-AS1 depletion repressed NSCLC cell 
      malignant phenotypes, in vivo tumor growth, and liver metastasis. 
      Mechanistically, AlkB homolog 5 (ALKBH5) enhanced CALML3-AS1 stability via 
      N(6)-methyladenosine (m(6)A) demethylation, whereas m(6)A reader YTH 
      domain-containing 2 (YTHDC2) destabilized CALML3-AS1. Moreover, CALML3-AS1 
      inhibited BTNL9 transcription and expression through the recruitment of Zeste 
      homolog 2 (EZH2). Rescue experiments demonstrated that BTNL9 downregulation 
      counteracted sh-CALML3-AS1-mediated antitumor effects on NSCLC. Taken together, 
      CALML3-AS1 modulated by ALKBH5 and YTHDC2 in an m(6)A modification dependent 
      manner drives NSCLC progression via epigenetically repressing BTNL9.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Zhang, Heng
AU  - Zhang H
AUID- ORCID: 0000-0002-1554-2051
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Changsha, 410008, Hunan Province, P. R. China. 404346@csu.edu.cn.
AD  - Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, 
      410008, Hunan Province, P. R. China. 404346@csu.edu.cn.
AD  - National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), 
      Changsha, 410008, Hunan Province, P. R. China. 404346@csu.edu.cn.
FAU - Wang, Shao-Qiang
AU  - Wang SQ
AD  - Department of Thoracic Surgery, Weifang People's Hospital, Weifang Medical 
      University, Weifang, 261041, Shandong Province, P.R. China.
AD  - Department of Scientific Research Management, Weifang People's Hospital, Weifang 
      Medical University, Weifang, 261041, Shandong Province, P.R. China.
FAU - Zhu, Jie-Bo
AU  - Zhu JB
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Changsha, 410008, Hunan Province, P. R. China.
FAU - Wang, Li-Na
AU  - Wang LN
AD  - Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, 
      Jining, 272029, Shandong Province, P. R. China.
FAU - Lin, Hang
AU  - Lin H
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Changsha, 410008, Hunan Province, P. R. China.
FAU - Li, Lin-Feng
AU  - Li LF
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Changsha, 410008, Hunan Province, P. R. China.
FAU - Cheng, Yuan-Da
AU  - Cheng YD
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Changsha, 410008, Hunan Province, P. R. China.
FAU - Duan, Chao-Jun
AU  - Duan CJ
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Changsha, 410008, Hunan Province, P. R. China.
FAU - Zhang, Chun-Fang
AU  - Zhang CF
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Changsha, 410008, Hunan Province, P. R. China. zhcf3801@csu.edu.cn.
AD  - Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, 
      410008, Hunan Province, P. R. China. zhcf3801@csu.edu.cn.
AD  - National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), 
      Changsha, 410008, Hunan Province, P. R. China. zhcf3801@csu.edu.cn.
AD  - Hunan Engineering Research Center for Pulmonary Nodules Precise Diagosis & 
      Treatment, Changsha, 410008, Hunan Province, P. R. China. zhcf3801@csu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231027
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (BTNL9 protein, human)
RN  - 0 (Butyrophilins)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
SB  - IM
MH  - Humans
MH  - Butyrophilins/genetics/metabolism
MH  - *Carcinoma, Non-Small-Cell Lung/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/genetics/pathology
MH  - Methylation
MH  - *MicroRNAs/genetics
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - *RNA Methylation/genetics
EDAT- 2023/10/27 00:42
MHDA- 2023/12/17 09:46
CRDT- 2023/10/26 23:28
PHST- 2023/04/17 00:00 [received]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2023/08/31 00:00 [revised]
PHST- 2023/12/17 09:46 [medline]
PHST- 2023/10/27 00:42 [pubmed]
PHST- 2023/10/26 23:28 [entrez]
AID - 10.1038/s41417-023-00670-7 [pii]
AID - 10.1038/s41417-023-00670-7 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2023 Dec;30(12):1649-1662. doi: 10.1038/s41417-023-00670-7. 
      Epub 2023 Oct 27.