Citation

  • Authors: Zheng Y. et al.. et al.
  • Year: 2021
  • Journal: J Cancer 12 1231-1239
  • Applications: in vitro / siRNA / INTERFERin
  • Cell types:
    1. Name: HGC-27
      Description: Human stomach carcinoma, undifferenciated
      Known as: HGC27
    2. Name: MGC-803
      Description: Human gastric carcinoma
      Known as: MGC803
    3. Name: OE33

Method

Human MGC80-3, HGC-27 and OE33 cells were seeded in a 12 well plate and transfected with 10nM miR-1262 mimics, miR-1262 inhibitors, ULK1 siRNAs or NC RNA (Genepharma) with INTERFERin® (Polyplus). Cells were harvested and counted at 24h, 48h and 72h after transfection.

Abstract

Gastric cardia adenocarcinoma (GCA) is one of two main gastric cancer subtypes and has its own epidemiological, pathogenic and clinical characteristics. Genetic polymorphisms locating in a microRNA (miRNA) gene enhancer could transcriptionally regulates miRNA expression via impacting binding of transcriptional factors. It is still unclear how miR-1262 and a potential regulatory rs12740674 polymorphism mapping to a strong enhancer region of miR-1262 contribute to GCA development. We genotyped miR-1262 rs12740674 in two independent case-control sets consisting of 1,024 GCA patients and 1,118 controls, and found that the rs12740674 CT or TT genotype carriers had a 0.69-fold decreased risk to develop GCA compared to the CC genotype carriers (95% confidence interval=0.57-0.84, P=2.1×10-4). In the genotype-phenotype correlation analyses of 21 pairs of GCA-normal tissues, the rs12740674 CT or TT genotype was associated with significantly increased levels of miR-1262. Cell proliferation, wound healing and transwell assays elucidated that miR-1262 is a novel GCA tumor suppressor. Consistently, a significantly down-regulated level of miR-1262 exists in GCA specimens compared to normal tissues. Furthermore, multiple lines of evidences indicated that oncogene ULK1 is the target gene of miR-1262 in GCA. Our findings demonstrate miR-1262 transcriptionally modulated by an enhancer genetic variant suppresses GCA via targeting oncogene ULK1. Our data highlight miR-1262 as a promising diagnostic marker and therapeutic target for GCA.

Pubmed