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Background: Gastric cancer is one of the most common malignancies worldwide. Recent studies have shown that microRNAs play crucial roles in regulating cellular proliferation process in gastric cancer. MicroRNA-29c (miR-29c) acts as a tumor suppressor in different kinds of tumors., Methods: Quantitative PCR was performed to evaluate miR-29c expression level in 67 patient gastric cancer tissues and 9 gastric cancer cell lines. The effects of miR-29c were explored by proliferation assay, soft agar colony formation assay, apoptosis and cell cycle analysis using flow cytometry. The target gene was predicted by bioinformatic algorithms and validated by dual luciferase reporter assay and Western blot analysis., Results: In this study, we demonstrate that miR-29c is down-regulated in gastric cancer tissues and cell lines. We indicate that overexpression of miR-29c inhibits cell proliferation, promotes apoptosis and arrests cell cycle at G1/G0 phase. We additionally show that miR-29c exerts these effects by targeting Nuclear autoantigenic sperm protein (NASP). Moreover, depletion of NASP can elite the phenotypes caused by miR-29c., Conclusions: These data suggest that miR-29c inhibits proliferation in gastric cancer and could potentially serve as an early biomarker and a novel therapy target.

MicroRNAs (miRNAs) have been widely accepted as a class of gene expression regulators which post-translationally regulate protein expression. These small noncoding RNAs have been proved closely involved in the modulation of various pathobiological processes in cancer. In this research, we demonstrated that miR-148a expression was significantly down-regulated in gastric cancer tissues in comparison with the matched normal mucosal tissues, and its expression was statistically associated with lymph node metastasis. Ectopic expression of miR-148a inhibited tumor cell proliferation and migration in vitro, and inhibited tumor formation in vivo. Subsequently, we identified cholecystokinin B receptor (CCK-BR) as a direct target of miR-148a using western blot and luciferase activity assay. More importantly, siRNA-induced knockdown of CCK-BR elicited similar anti-oncogenic effects (decreased proliferation and migration) as those induced by enforced miR-148a expression. We also found that miR-148a-mediated anti-cancer effects are dependent on the inhibition of STAT3 and Akt activation, which subsequently regulates the pathways involved in cell proliferation and migration. Taken together, our results suggest that miR-148a serves as a tumor suppressor in human gastric carcinogenesis by targeting CCK-BR via inactivating STAT3 and Akt.

Accumulating evidence has indicated that microRNAs (miRNAs) act as critical epigenetic regulators in tumor carcinogenesis. Here, we report that miR-199a-3p was significantly upregulated in gastric cancer (GC) cell lines and tissues. Functional studies demonstrated that miR-199a-3p dramatically increased cell proliferation and suppressed cell apoptosis both in vitro and in vivo. Furthermore, the transcriptional regulator zinc fingers and homeoboxes 1 (ZHX1) was identified as one of the direct downstream targets of miR-199a-3p, miR-199a-3p bound to the ZHX1 3′ untranslated region (3′UTR) to regulate ZHX1 protein expression. In addition, the expression of miR-199a-3p was inversely associated with that of ZHX1 in GC cell lines. Overexpression of miR-199a-3p in SGC-7901 cells inhibited ZHX1 expression, while reduction in miR-199a-3p by inhibitors in NCI-N87 cells enhanced ZHX1 expression. Moreover, restoring ZHX1 expression in SGC-7901/miR-199a-3p cells inhibited the cell proliferation induced by miR-199a-3p. Taken together, these findings suggest that miR-199a-3p may function as a novel tumor promoter in GC and its oncogenic activity may involve the direct targeting and inhibition of ZHX1.

Background: microRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests miR-24 plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-24 in gastric cancer (GC)., Methods: The expression of miR-24 in GC tissues compared with matched non-tumor tissues and GC cells was detected by qRT-PCR. Synthetic short single or double stranded RNA oligonucleotides and lentiviral vectors were used to regulate miR-24 expression in GC cells to investigate its function in vitro and in vivo., Results: miR-24 was significantly downregulated in GC tissues compared with matched non-tumor tissues and was associated with tumor differentiation. Ectopic expression of miR-24 in SGC-7901 GC cells suppressed cell proliferation, migration and invasion in vitro as well as tumorigenicity in vivo by inducing cell cycle arrest in G0/G1 phase and promoting cell apoptosis. Furthermore, we identified RegIV as a target of miR-24 and demonstrated that miR-24 regulated RegIV expression via binding its 3' untranslated region., Conclusions: miR-24 functions as a novel tumor suppressor in GC and the anti-oncogenic activity may involve its inhibition of the target gene RegIV. These findings suggest the possibility for miR-24 as a therapeutic target in GC.

Background: Emerging evidence has shown that microRNAs are involved in gastric cancer development and progression. Here we examine the role of miR-133b in gastric cancer., Methods: Quantitative real-time PCR analysis was performed in 140 patient gastric cancer tissues and 8 gastric cancer cell lines. The effects of miR-133b in gastric cancer cells metastasis were examined by scratch assay, transwell migration and matrigel invasion. In vivo effects of miR-133b were examined in an intraperitoneal mouse tumor model. Targets of miR-133b were predicted by bioinformatics tools and validated by luciferase reporter analyses, western blot, and quantitative real-time PCR., Results: MiR-133b was significantly downregulated in 70% (98/140) of gastric cancer patients. Expression of miR-133b was negatively correlated with lymph node metastasis of gastric cancer in patients. Similarly, the expression of miR-133b was significantly lower in seven tested gastric cancer cell lines than in the immortalized non-cancerous GES-1 gastric epithelial cells. Overexpression of miR-133b markedly inhibited metastasis of gastric cancer cells in vitro and in vivo. Moreover, the transcriptional factor Gli1 was identified as a direct target for miR-133b. Level of Gli1 protein but not mRNA was decreased by miR-133b. Activity of luciferase with Gli1 3'-untranslated region was markedly decreased by miR-133b in gastric cancer cells. Gli1 target genes, OPN and Zeb2, were also inhibited by miR133b., Conclusions: MiR-133b is frequently decreased in gastric cancer. Overexpression of miR-133b inhibits cell metastasis in vitro and in vivo partly by directly suppressing expression of Gli1 protein. These results suggested that miR-133b plays an important role in gastric cancer metastasis.

V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family and act as an adaptor protein participating in intra-cellular signal transduction. The role of CRKL in gastric cancer (GC) remains unclear. In this study, we show that CRKL was aberrantly highly expressed in both GC tumor specimens and cell lines (SGC-7901, MKN-45, MKN-28 and SUN-16). The expression of CRKL was significantly correlated with GC clinicopathologic features including tumor size, local invasion, lymph node metastasis and TNM stages. Knock-down of CRKL in SGC-7901 cells induced a suppression of cell proliferation along with a significant arrest of cell cycle in G0/G1 phase, however, no significant influence was observed on cell apoptosis. We validate that miR-126, a suppressor in GC, was a negative regulator of CRKL by directly combining with the 3' untranslated region of CRKL mRNA, and over-expression of miR-126 inhibited the protein expression of CRKL significantly. These results suggest that CRKL may function as an oncogene in GC by promoting the GC cell proliferation, which provides us a likely biomarker and a potential target for GC prevention, diagnosis and therapeutic treatment. Moreover, the targeting relationship between CRKL and miR-126 partly reveals the mechanism of miR-126 on GC suppression., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: MicroRNAs can promote or suppress the evolution of malignant behaviors by regulating multiple targets. We aimed to determine the expression of miR-301a recently screened in gastric cancer, to investigate the biological effects of miR-301a and to identify the specific miR-301a target gene., Methods: Quantitative real-time RT-PCR was used to test miR-301a expression. Functional effects were explored by a water-soluble tetrazolium salt assay, a colony formation assay in soft agar, a migration assay, an invasion assay and cytometry used to determine apoptosis and cell cycle. Nude mice were inoculated subcutaneously by retrovirus-mediated stably expressed SGC-7901 cells. The target gene was determined by bioinformatic algorithms, dual luciferase reporter assay and Western blot., Results: Firstly, we found that miR-301a was significantly upregulated both in cells and tissues of gastric cancer. The expression level of miR-301a was inversely correlated with tumor differentiation of gastric cancer tissues. Secondly, miR-301a promoted cell growth, soft agar clonogenicity, migration, invasion, and decreased cell apoptosis induced by cisplatin in vitro, while blockage of miR-301a reduced the percentage of G2/M phase cells via flow cytometry in gastric cancer cells. Ectopic expression of miR-301a enhanced the subcutaneous tumorigenesis in vivo. Finally, miR-301a directly downregulated RUNX3 expression post-transcriptionally in gastric cancer., Conclusion: Our results demonstrate that miR-301a plays important roles in the development of gastric cancer.

Emerging studies have indicated that microRNAs are involved in the development and progression of cancer. Here we found that miR-202-3p was frequently down-regulated in gastric cancer tissues. Overexpression of miR-202-3p in gastric cancer cells MKN-28 and BGC-823, markedly suppressed cell proliferation and induced cell apoptosis both in vitro and in vivo. Furthermore, Gli1 expression was frequently positive in gastric cancer tissues and inversely correlated with miR-133b expression. We demonstrate that the transcriptional factor Gli1 was a target of miR-202-3p and plays an essential role as a mediator of the biological effects of miR-202-3p in gastric cancer. MiR-202-3p also inhibited the expression of γ-catenin and BCL-2. Taken together, these findings suggest that miR-202-3p may function as a novel tumor suppressor in gastric cancer and its anti-tumor activity may attribute the direct targeting and inhibition of Gli1.

MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.

Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Here, we report that expression of miR-625 is significantly down-regulated and negatively correlated with lymph node metastasis in gastric cancer. miR-625 significantly inhibits invasion and metastasis of gastric cancer cells both in vitro and in vivo. Moreover, we identify that ILK is a direct target gene for miR-625 and knockdown of ILK has a phenocopy of overexpression of miR-625. Taken together, our findings suggest that miR-625 plays an important role in the mechanism of tumor metastasis., (Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Emerging evidence has indicated microRNAs are involved in tumor development and progression, acting as tumor suppressors or oncogenes. Here we report that miR-409-3p was significantly downregulated in gastric cancer (GC) cell lines and tissues. Overexpression of miR-409-3p in SGC-7901 gastric cancer cells dramatically suppressed cell proliferation and induced cell apoptosis both in vitro and in vivo. Furthermore, we demonstrate that the transcriptional regulator PHF10 was a target of miR-409-3p. Taken together, these findings suggest that miR-409-3p may function as a novel tumor suppressor in GC and its anti-oncogenic activity may involve the direct targeting and inhibition of PHF10., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

MicroRNAs have emerged as important gene regulators and are recognised as key players in carcinogenesis. In the present study, we show that miR-126 was significantly down-regulated in gastric cancer tissues compared with matched normal tissues and was associated with clinicopathological features, including tumour size, lymph node metastasis, local invasion and tumour-node-metastasis (TNM) stage. Ectopic expression of miR-126 in SGC-7901 gastric cancer cells potently inhibited cell growth by inducing cell cycle arrest in G0/G1 phase, migration and invasion in vitro as well as tumorigenicity and metastasis in vivo. Mechanistically, we identified the adaptor protein Crk as a target of miR-126. Taken together, our results suggest that miR-126 may function as a tumour suppressor in gastric cancer, with Crk as a direct target., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)