Back to Search
Start Over
ALKBH5 promotes invasion and metastasis of gastric cancer by decreasing methylation of the lncRNA NEAT1
- Source :
- Journal of Physiology and Biochemistry
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- N6-Methyladenosine (m6A) is the most common posttranscriptional modification of RNA and plays critical roles in cancer pathogenesis. However, the biological function of long noncoding RNA (lncRNA) methylation remains unclear. As a demethylase, ALKBH5 (alkylation repair homolog protein 5) is involved in mediating methylation reversal. The purpose of this study was to investigate lncRNA m6A modification and its role in gastric cancer (GC). Bioinformatics predicted interactions of ALKBH5 with lncRNAs. Five methods were employed to assess the function of nuclear paraspeckle assembly transcript 1 (NEAT1), including gene silencing, RT-PCR, separation of nuclear and cytoplasmic fractions, scrape motility assays, and transwell migration assays. Then, m6A RNA immunoprecipitation and immunofluorescence were used to detect methylated NEAT1 in GC cells. Rescue assays were performed to define the relationship between NEAT1 and ALKBH5. NEAT1 is a potential binding lncRNA of ALKBH5. NEAT1 was overexpressed in GC cells and tissue. Additional experiments confirmed that knockdown of NEAT1 significantly repressed invasion and metastasis of GC cells. ALKBH5 affected the m6A level of NEAT1. The binding of ALKBH5 and NEAT1 influences the expression of EZH2 (a subunit of the polycomb repressive complex) and thus affects GC invasion and metastasis. Our findings indicate a novel mechanism by which ALKBH5 promotes GC invasion and metastasis by demethylating the lncRNA NEAT1. They may be potential therapeutic targets for GC.
- Subjects :
- 0301 basic medicine
Physiology
Nuclear paraspeckle assembly transcript 1
030209 endocrinology & metabolism
Methylation
Biochemistry
Long noncoding RNAs
03 medical and health sciences
0302 clinical medicine
Cell Movement
Stomach Neoplasms
Cell Line, Tumor
Humans
Gene silencing
Enhancer of Zeste Homolog 2 Protein
Neoplasm Invasiveness
Alkylation repair homolog protein 5
Gene knockdown
biology
Chemistry
EZH2
AlkB Homolog 5, RNA Demethylase
RNA
Paraspeckle
General Medicine
Long non-coding RNA
Gene Expression Regulation, Neoplastic
N6-Methyladenosine
030104 developmental biology
Cancer research
biology.protein
Demethylase
RNA, Long Noncoding
Original Article
Gastric cancer
Subjects
Details
- ISSN :
- 18778755 and 11387548
- Volume :
- 75
- Database :
- OpenAIRE
- Journal :
- Journal of Physiology and Biochemistry
- Accession number :
- edsair.doi.dedup.....3c29988f3d5a72be24d2a25008a48a7f