MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A

Abstract

MicroRNAs (miRNAs) are a type of small noncoding RNAs that are strongly implicated in carcinogenesis. However, the potential diagnostic, prognostic and therapeutic roles of the majority of miRNAs in the pathological processes of tumorigenesis remain largely unknown. Our and others' data revealed that miR-204-5p was significantly downregulated in gastrointestinal tumor tissues compared with adjacent noncancerous tissues. The downregulation of miR-204-5p was confirmed in our gastric cancer (GC) cohort, and we showed that ectopic expression of miR-204-5p inhibited, whereas silencing miR-204-5p expression promoted GC cell proliferation in vitro. Subsequent mechanistic investigations identified that USP47 and RAB22A are direct functional targets of miR-204-5p in GC. Silencing the expression of USP47 and RAB22A using siRNA phenocopied the proliferation-inhibiting function of miR-204-5p in GC cells. Our results uncovered that miR-204-5p acts as a tumor suppressor in GC through inhibiting USP47 and RAB22A.

Reduced expression of serum miR-204 predicts poor prognosis of gastric cancer

“…The expression level of miR-204 has been reported to be downregulated in GC tissues and cell lines by different research groups (Zhang et al, 2013(Zhang et al, , 2015a. Zhang et al (2015a) showed that miR-204-5p suppression could promote the proliferative capacity of GC cell lines, whereas forced expression of miR-204 inhibited this capacity. In addition, USP47 and RAB22A were identified as direct functional targets of miR-204-5p in GC (Zhang et al, 2015a).…”

“…Zhang et al (2015a) showed that miR-204-5p suppression could promote the proliferative capacity of GC cell lines, whereas forced expression of miR-204 inhibited this capacity. In addition, USP47 and RAB22A were identified as direct functional targets of miR-204-5p in GC (Zhang et al, 2015a). An inverse relationship was found between miR-204 expression and SIRT-1 expression in GC tissues, and overexpression of miR-204 was found to reduce GC cell invasion, anoikis resistance, and epithelial-mesenchymal transition by targeting SIRT-1 at the post-transcriptional level.…”

“…Although miR-204 has been found to be downregulated in GC tissues (Zhang et al, 2015a), its expression profile in serum samples and its potential for clinical use are unknown. Therefore, the purpose of the current study was to investigate the clinical significance of serum miR-204 for GC.…”

Histological and Pathological Assessment of miR-204 and SOX4 Levels in Gastric Cancer Patients

“…miRNAs directly interact with the mRNA 3′ untranslated regions (3′UTR) of their target genes including oncogenes and tumor suppressing genes and usually negatively regulate them [11, 12]. In gastric cancer, miR-144, miR-449a, miR-141, miR-361, and so forth were reported to suppress the oncogenicity of tumors [13–16], and miR-19a, miR-223, miR-425, and so forth were demonstrated to promote the oncogenicity of tumors [17–19].…”

“…In gastric cancer, miR-144, miR-449a, miR-141, miR-361, and so forth were reported to suppress the oncogenicity of tumors [13–16], and miR-19a, miR-223, miR-425, and so forth were demonstrated to promote the oncogenicity of tumors [17–19]. MiR-204 is one of the miRNAs that have been determined to suppress tumor initiation and development in lung cancer, esophageal cancer, gastric cancer, and other cancers [11, 20, 21]. USP47, RAB22A, SIRT1, Snai1, and so forth are targets of miR-204 that mediate miR-204 reducing the oncogenicity of gastric cancer [11, 22, 23].…”