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MicroRNAs (miRs) can affect the progression of cervical cancer (CC). The present study investigated the function of miR‑145‑5p in CC and demonstrated its association with fascin (FSCN1). The expression levels of miR‑145‑5p in CC tissues and cell lines were analyzed using reverse transcription‑quantitative PCR, and its direct targets were explored using a luciferase reporter assay. The viability, migration and invasion of HeLa cells transfected with small interfering FSCN1 or with miR‑145‑5p mimics and inhibitors were analyzed using Cell Counting Kit‑8 and Transwell assays. The expression levels of FSCN1 mRNA and protein were investigated using reverse transcription PCR and western blotting. miR‑145‑5p was downregulated in CC tissues and cell lines. Moreover, overexpression of miR‑145‑5p inhibited the migration, invasion and viability of HeLa cells. miR‑145‑5p directly targeted FSCN1, which regulated the suppressive functions of miR‑145‑5p in CC cells. Overall, miR‑145‑5p is a tumor suppressor gene and a promising target for CC treatment.

Fascin actin-bundling protein 1 (FSCN1) is associated with tumor progression. In addition, deregulation of the expression of FSCN1 has been observed in certain types of cancer. However, the detailed role of FSCN1 in gastric cancer remains to be elucidated. In the present study, downregulation of microRNA (miR)-133a and upregulation of FSCN1 were both observed in gastric cancer tissues and cell lines. Functional studies have revealed that miR-133a is able to bind to the 3'-untranslated region of FSCN1 mRNA, and overexpression of miR-133a causes downregulation of FSCN1 expression, while downregulation of miR-133a leads to an increased FSCN1 expression in gastric cancer cells. Furthermore, overexpression of miR-133a inhibited proliferation and invasion, but promoted apoptosis of gastric cancer cells, which may be reversed by upregulation of FSCN1. By contrast, downregulation of miR-133a enhanced proliferation and invasion, but suppressed apoptosis in gastric cancer cells. In conclusion, the anti-oncogenic activity of miR-133a may involve the inhibition of the target gene FSCN1. The present study suggested that miR-133a may be a potential therapeutic target in the treatment of gastric cancer.

Colorectal cancer (CRC) is the most frequently diagnosed malignancy of the gastrointestinal tract. The dysregulation of microRNAs (miRNAs/miRs) has been reported in the majority of types of human cancer, and is correlated with tumorigenesis and tumor development. Abnormal expression of miR‑663 has been observed in various types of human cancer. However, little is known about its role in CRC. Therefore, the aim of the present study was to clarify the expression and potential role of miR‑663, and its underlying molecular mechanism in CRC. It was observed that miR‑663 was markedly downregulated in CRC tissues and cell lines. Decreased miR‑663 expression levels in CRC tissues were correlated with tumor, node, metastasis stage and lymph node metastasis. Functional assays revealed that upregulation of miR‑663 inhibited cell proliferation and invasion in CRC. Further molecular mechanism assays demonstrated the fascin (FSCN1) was a target gene of miR‑663. In addition, FSCN1 was increased and negatively correlated with miR‑663 expression in CRC tissues. FSCN1 underexpression mimicked the tumor suppressive functions induced by miR‑663 overexpression on CRC cell proliferation and invasion. Collectively, the present study presented evidence that miR‑663 may act as a tumor suppressor in CRC by directly targeting FSCN1, which may lead to a potential therapeutic strategy focusing on miR‑663 and FSCN1 for patients with this disease.

Uveal melanoma (UM) is characterized by high metastasis and poor prognosis. A more improved understanding of the metastatic mechanism in UM cells is essential for the design of molecular therapy. Grb2-associated binder 2 (Gab2) has been reported to serve important roles in the progression of various types of human cancer. However, the role of Gab2 in the migration and invasion of UM remains unclear. The present study sought to further assess the expression of Gab2 in UM and the role of Gab2 in the invasion of UM cells. Clinical UM tissue samples and UM cell lines were analyzed using western blot analysis for the expression of Gab2. RNA interference was used to investigate the effect of Gab2 on the migratory and invasive characteristics of UM cells in vitro. The expression levels of matrix metalloproteinase (MMP)2, MMP9 and fascin in Gab2-knockdown, and control cells were also detected using western blot analysis. A total of 20 clinical UM samples and a subset of UM cell lines were investigated with uniformly high Gab2 expression. In the in vitro experiment, reduction of Gab2 using small interfering RNA inhibited the migration and invasion of UM cells by mediating MMPs, and fascin expression. These data suggest that Gab2 is a useful prognostic marker for UM and a novel therapeutic target for UM metastasis intervention.

The key molecular events that contribute to tumorigenesis are incompletely understood. The aim of the present study was to characterize and compare the biological phenotypes of three human telomerase reverse transcriptase (hTERT) and/or human papillomavirus 16 E6 and E7‑immortalized esophageal epithelial cell lines, NE2‑hTERT (NE2), NE3‑E6E7‑hTERT (NE3) and NEcA6‑E6E7‑hTERT (NEcA6). The present study used soft‑agar colony formation assays, tumorigenicity assays in nude mice, and cell proliferation, adhesion and migration assays to identify the biological characteristics of NE2, NE3 and NEcA6 cells. NE2 and NE3 cells exhibited characteristics of benign cells, such as the inability to grow in soft agar or form tumors in nude mice. By contrast, NEcA6 cells had undergone transformation, as demonstrated by the ability to grow in soft agar and form tumors in nude mice. In addition, NEcA6 cells exhibited increased migration and adhesion capabilities when compared with NE2 and NE3 cells. In order to identify mechanism(s) that may contribute to the altered biological phenotypes exhibited by these cells, the expression of three proteins involved in modulating cell migration [fascin, ezrin/radixin/moesin family proteins and phosphorylated‑focal adhesion kinase (Tyr 397)], as well as the expression status and subcellular localization of three key focal adhesions components (paxillin, talin and kindlin‑2) were examined. Paxillin, talin and kindlin‑2 were localized to adhesive sites that connect F‑actin with the extracellular matrix in transformed NEcA6 cells, but were distributed in a diffuse manner in NE2 and NE3 cells. Knockdown of kindlin‑2 in NE3 and NEcA6 cells decreased cell adhesion, however, NEcA6 cells demonstrated a greater sensitivity to knockdown of kindlin‑2. No significant differences were observed in the protein expression levels of fascin, exrin/radixin/moesin and p‑FAK in the three cell lines. In conclusion, these results demonstrate that these three focal adhesion components, particularly kindlin‑2, may contribute to the carcinogenesis of esophageal squamous cells.

Distant metastasis of non-small cell lung cancer (NSCLC) leads to high postoperative recurrence and low long‑term survival rates. Deregulation of microRNA (miR)-200b has been demonstrated to be associated with NSCLC metastasis. However, the underlying molecular mechanism of miR‑200b in mediating NSCLC cell migration and invasion remains to be fully elucidated. In the current study, reverse transcription‑quantitative polymerase chain reaction data indicated that miR‑200b was significantly downregulated in several NSCLC cell lines, including A549, L78, H1229, H358 and H1650, compared with a normal human lung epithelial cell line, BEAS‑2B. Overexpression of miR‑200b significantly inhibited NSCLC cell migration and invasion. Bioinformatics analysis and a luciferase reporter assay were additionally conducted, which identified fascin actin‑bundling protein 1 (FSCN1) as a novel target of miR‑200b. In addition, miR‑200b negatively mediated the protein expression of FSCN1 in NSCLC H1229 cells. siRNA‑mediated FSCN1 inhibition also significantly inhibited the migration and invasion of H1229 cells. In addition, overexpression of FSCN1 effectively reversed the suppressive effect of miR‑200b overexpression on NSCLC cell migration and invasion. Accordingly, it is suggested that miR‑200b is able to inhibit the migration and invasion of NSCLC cells, partly at least, via targeting FSCN1. The current study provides novel insight into miR‑200 regulation in NSCLC metastasis.

MicroRNA (miR)‑145 has been demonstrated to act as a tumor suppressor, and deregulation of fascin 1 (FSCN1) has been observed in several types of human malignancy, including gastric carcinoma. However, the molecular mechanism underlying the function of miR‑145, specifically its targets in gastric carcinoma have yet to be fully elucidated. In the present study, downregulation of miR‑145 and upregulation of FSCN1 was identified in gastric carcinoma cell lines, compared with normal gastric mucosal epithelial cells. A luciferase reporter assay demonstrated that miR‑145 was able to bind to the 3'‑untranslated region of FSCN1 mRNA. Overexpression of miR‑145 led to a significant decrease in FSCN1 expression levels, whereas knockdown of miR‑145 resulted in increased FSCN1 expression levels in gastric carcinoma cells. Furthermore, overexpression of miR‑145 inhibited proliferation, migration and invasion in gastric carcinoma cells. Similar effects were also observed in gastric carcinoma cells transfected with FSCN1 small interfering RNA. In addition, overexpression of FSCN1 reversed the suppressive effects of miR‑145 upregulation on proliferation, migration and invasion in gastric carcinoma cells, suggesting that FSCN1 is indeed involved in the miR‑145‑mediated malignant phenotype of gastric carcinoma cells. The present study revealed an anti‑oncogenic role of miR‑145 in gastric carcinoma via inhibition of FSCN1, and suggested that miR‑145 may be used for the treatment of gastric carcinoma.

Fascin actin-bundling protein 1 (FSCN1) is associated with tumor progression. In addition, deregulation of the expression of FSCN1 has been observed in certain types of cancer. However, the detailed role of FSCN1 in gastric cancer remains to be elucidated. In the present study, downregulation of microRNA (miR)-133a and upregulation of FSCN1 were both observed in gastric cancer tissues and cell lines. Functional studies have revealed that miR-133a is able to bind to the 3'-untranslated region of FSCN1 mRNA, and overexpression of miR-133a causes downregulation of FSCN1 expression, while downregulation of miR-133a leads to an increased FSCN1 expression in gastric cancer cells. Furthermore, overexpression of miR-133a inhibited proliferation and invasion, but promoted apoptosis of gastric cancer cells, which may be reversed by upregulation of FSCN1. By contrast, downregulation of miR-133a enhanced proliferation and invasion, but suppressed apoptosis in gastric cancer cells. In conclusion, the anti-oncogenic activity of miR-133a may involve the inhibition of the target gene FSCN1. The present study suggested that miR-133a may be a potential therapeutic target in the treatment of gastric cancer.

Fascin 1 (fascin) is known to be overexpressed in esophageal squamous cell carcinoma (ESCC); however, the mechanisms of this overexpression are unclear. In this study, the FSCN1 core promoter was isolated and the transcriptional regulatory mechanism of fascin overexpression in ESCC was investigated. By combining the use of progressive 5' deletions and dual-luciferase reporter assays, the FSCN1 core promoter was identified within the -74/-41 region in esophageal carcinoma EC109 cells harboring a GC box and a composite CRE/AP-1 binding site. Further analysis demonstrated that only the GC box was essential for transcription. No methylated CpG sites were found within the FSCN1 promoter in normal and tumor cells or tissues examined by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS), which suggested that hypomethylation did not contribute to the overexpression of fascin in ESCC. Furthermore, the region of +168/+2838 was found to inhibit promoter activity. Additional BGS analysis indicated that the region of +560/+859 (in exon 1) was hypermethylated in normal and tumor cells or tissues. Unexpectedly, demethylation did not eliminate the suppression, suggesting that a silencer caused this suppression, and not DNA methylation in exon 1. Taken together, the results indicate that fascin overexpression in ESCC is regulated by the transactivation of the fascin promoter, but not by its hypomethylation.