Impairment of growth of gastric carcinoma by miR-133-mediated Her-2 inhibition

Abstract

Gastric carcinoma (GC) is a leading cause of cancer-related death in China. Dysregulation of microRNAs (miRNAs) has been shown to contribute to the development of GC, whereas the role of miR-133 in GC is unknown. Here, we analyzed the levels of miR-133 in GC tissues by reverse and quantitative transcription polymerase chain reaction (RT-qPCR). We overexpressed or inhibited miR-133 in GC cells. Cell growth was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis was evaluated by fluorescence-activated cell sorting (FACS) analysis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual-luciferase reporter assay. We detected lower miR-133 levels in GC tissues compared with normal gastric tissue. Moreover, the low miR-133 levels were correlated with low survival rate. Overexpression of miR-133 inhibited cell growth and promoted apoptosis, while depletion of miR-133 increased cell growth and suppressed apoptosis. Moreover, the 3'-untranslated region (3'UTR) of Her-2, the epidermal growth factor receptor (EGFR) that transduces cell growth signals, appeared to be targeted by miR-133. Together, these data suggest that reduced miR-133 levels in GC tissues promote GC growth, which possibly contributes to a low survival rate of GC patients. MiR-133 may target Her-2 to suppress GC cell growth.

miR-133 inhibits pituitary tumor cell migration and invasion via down-regulating FOXC1 expression

“…It has been reported that miR-132, miR-15a, and miR-16 can suppress the migration and invasion of pituitary tumor cells during its metastasis (Bottoni et al, 2007;Palumbo et al, 2013). miR-133 is relatively less studied but, recently, a potential role for miR-133 in gastric cancer and its molecular mechanisms have been reported (Zhang et al, 2015).…”

“…One of these miRs, miR-133, has been shown to play a role in tumor suppression in a variety of cancers, including inhibiting breast cancer cell migration and invasion, gastric cancer cell growth and migration, and liver fibrosis (Esquela- Kerscher and Slack, 2006;Cheng et al, 2012;Liu et al, 2014;Mei et al, 2014;Wang et al, 2014;Yongchun et al, 2014;Xie et al, 2015;Zhang et al, 2015). Recent studies have shown that miRs may be a new regulatory mechanism involved in the onset of pituitary adenoma, providing a new method for the diagnosis and treatment of pituitary adenoma (Trivellin et al, 2012;Gadelha et al, 2013;Di Ieva et al, 2014;Leone et al, 2014).…”

Insights into roles of the miR-1, -133 and -206 family in gastric cancer (Review)

“…This result was confirmed in GC cell lines and primary GC tissues by both microarray and qPCR methods. The level of miR-133 in GC and corresponding non-tumour tissues was detected in three different groups of GC patients independently (59)(60)(61). Results further revealed that miR-133 reduction is more likely to perform worse in tumour size, invasion depth and peripheral organ metastasis.…”

“…Dysfunction of miR-133 was an independent prognosis factor for overall survival (60,61). Moreover, by luciferase assay, miR-133 was proved to target 3'UTR of EGFR and HER-2, which may cut cell growth signals off, and inhibits cell growth ultimately promoting apoptosis (59). These related research results of miR-133 in GC as a whole have elucidated a novel mechanism for oncogene inhibition by miRNA-mediated pathways and offer new avenues for GC treatment.…”

miR-455 inhibits cell proliferation and migration via negative regulation of EGFR in human gastric cancer

“…the carcinogenesis and development of gastric cancer. But few studies have revealed the relationship between miRNAs and EGFR in gastric cancer (16,17).…”