Published online Jul 15, 2023. doi: 10.4251/wjgo.v15.i7.1182
Peer-review started: December 7, 2022
First decision: January 18, 2023
Revised: March 30, 2023
Accepted: April 30, 2023
Article in press: April 30, 2023
Published online: July 15, 2023
Gastric cancer (GC) is a malignant tumor with high morbidity and mortality. Expression of COL5A2 is significantly elevated in GC. However, its specific regulatory mechanism has not been elucidated.
Abnormal expression of noncoding RNAs (ncRNAs) has been found in GC, including microRNA (miRNA) and long noncoding RNA (lncRNA). The ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC are not well understand.
To explore the competing endogenous RNA regulatory mechanism and immune mechanism of COL5A2 in GC.
StarBase was used to predict the interaction of miRNA–lncRNA or miRNA–mRNA in GC. The direct interaction between COL5A2, miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay. The correlation between of COL5A2 and macrophages infiltration was analyzed through bioinformatics and validated in paired GC tissues by immunohistochemical staining.
miR-144-3p interacted directly with COL5A2 and negatively regulated the expression of COL5A2. ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p, thus inhibiting the expression of miR-144-3p. Compared to paired normal tissue, COL5A2 expression was upregulated at the protein level, especially in the middle and late stages of GC. The high expression of COL5A2 was positively linked to macrophage infiltration in GC.
COL5A2 regulated by ENTPD1-AS1–miR-144-3p is associated with poor prognosis and macrophage infiltration in GC.
ENTPD1-AS1-miR-144-3p-COL5A2 might be a new therapeutic target for GC.