The role of microRNA-133b and its target gene FSCN1 in gastric cancer

Abstract

Background: Increasing evidences have documented that microRNAs (miRNAs) act as oncogenes or tumor suppressors in gastric cancer (GC). In this study, we aimed to investigate the expression of miR-133b in a large number of GC samples and elucidate its role in GC carcinogenesis and the detailed mechanism. Methods: We used Taqman probe stem-loop real-time PCR to accurately measure the levels of miR-133b in 100 pairs of gastric cancer tissues and the adjacent non-neoplastic tissues. miR-133b mimics were overexpressed in GC cell lines, miR-133b inhibitors were also introduced in GES cells to investigate its role on regulating cell proliferation, cell migration and cell invasion. The target of miR-133b was identified by luciferase reporter assay and western blot. Fascin actin-bundling protein 1 (FSCN1) siRNA was used to achieve the knockdown of FSCN1 in GC cells and to investigate its role on modulating GC cell proliferation and invasion. Results: miR-133b was significantly down-regulated in GC cell lines and in GC tissues compared with adjacent normal tissues. Moreover, lower-level of miR-133b was also associated with venous invasion and a more aggressive tumor phenotype. Re-introduction of miR-133b in GC cells can inhibit cell proliferation, cell migration and invasion. In contrary, knockdown of miR-133b in GES cells can promote cell proliferation and invasion. Further investigation indicated that miR-133b targeted FSCN1 in GC cells and knockdown of FSCN1 can also inhibit GC cell growth and invasion. Conclusion: Our findings demonstrated that miR-133b was significantly down-regulated in GC tissues and exerted its tumor suppressor role in GC cells. The investigation of the detailed mechanism showed that miR-133b directly targeted FSCN1 which functioned as an oncogenic gene in GC cells. These results suggested that miR-133b can be developed as a new diagnostic marker or therapeutic target for GC.

MicroRNA-133b inhibits the migration and invasion of non small cell lung cancer cells via targeting FSCN1

“…Therefore, FSCN1 is involved in the regulation of cell motility. In the present study, FSCN1 was notably upregulated in NSCLC cell lines, and the overexpression of FSCN1 reversed the suppressive effect of miR-133b overexpression on NSCLC cell migration and invasion, suggesting that FSCN1 plays an oncogenic role in NSCLC (23)(24)(25). Similar findings have also been reported in other types of human cancers; for instance, the knockdown of FSCN1 was found to inhibit the proliferation and invasion of gastric cancer cells (23).…”

“…In the present study, FSCN1 was notably upregulated in NSCLC cell lines, and the overexpression of FSCN1 reversed the suppressive effect of miR-133b overexpression on NSCLC cell migration and invasion, suggesting that FSCN1 plays an oncogenic role in NSCLC (23)(24)(25). Similar findings have also been reported in other types of human cancers; for instance, the knockdown of FSCN1 was found to inhibit the proliferation and invasion of gastric cancer cells (23). In addition, the inhibition of FSCN1 resulted in a reduced number of filopodia, an altered glioma cell shape, and inhibited the migration and invasion of glioma cells (24).…”

“…Previous studies have also reported that miR-133b negatively regulates the expression of FSCN1 in other types of human cancers, including esophageal squamous cell carcinoma (ESCC) and gastric cancer (23,26,27). Kano et al found that the overexpression of miR-133b inhibited ESCC cell proliferation and invasion, that FSCN1 was a target of miR-133b and that the knockdown of FSCN1 also suppressed ESCC cell proliferation and invasion (26).…”

XIAP 3′-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p

“…Of particular importance, our microarrays revealed an up-regulation of FSCN1 transcripts in XIAP 3′UTR cells. Several studies have reported that FSCN1 is highly expressed in malignant tumors, and is associated with increased cell motility and aggressive behavior of tumors [29, 37–39]. This is similar to the findings in breast cancer, where overexpression of FSCN1 was correlated with invasion and predicts poor survival [30].…”

Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression

“…miRNAs regulate gene expression via post-transcriptional gene silencing of messenger RNAs (mRNAs), potentially leading to mRNA degradation, with consequent inhibition of gene translation [12]. In gastric cancer, miR-133b acts as a tumor suppressor and negatively regulates FSCN1 expression [13]. Restoring the expression of miR-133b can inhibit the growth and invasion of colorectal cancer cells via directly targeting EGFR [14].…”