MicroRNA-203 suppresses gastric cancer growth by targeting PIBF1/Akt signaling.

BACKGROUND: MicroRNAs (miRNAs) have been proved involved in many tumorigenic behaviors including tumor growth. But, the clinical significance and functions of miRNA-203 in gastric cancer (GC) remain elusive. RESULTS: Decreased expression of miRNA-203 was correlated with tumor size, poor prognosis and recurrence in GC patients. Overexpression of miR-203 or knockdown of its target progesterone immunomodulatory binding factor 1 (PIBF1) inhibited GC growth in vitro and in vivo, while miR-203 knockdown promoted GC proliferation. In addition, PIBF1 overexpression attenuated the inhibitory effects of miR-203 on GC growth and enhanced that effect on p-Akt expression. CONCLUSIONS: MiR-203 as a tumor biomarker suppresses GC growth through targeting the PIBF1/Akt signaling, suggesting that it may have the important therapeutic potential for the treatment of GC.

Loss of large tumor suppressor 1 promotes growth and metastasis of gastric cancer cells through upregulation of the YAP signaling.

Accumulating evidence shows that large tumor suppressor 1 (LATS1) as a novel resident governor of cellular homeostasis is implicated in multiple tumorigenic properties including cell growth, apoptosis and metastasis. However, the contribution of LATS1 to gastric carcinoma (GC) remains unclear. The correlation of LATS1 expression with clinicopathologic characteristics, GC prognosis and recurrence was analyzed by immunohistochemistry, Univariate and Kaplan-Meier analysis. Functional experiments were performed to investigate biological behaviors of GC cells and underlying molecular mechanisms. Tumor growth and metastasis was assessed in vivo using orthotopic implantation GC models in severe combined immune deficiency (SCID) mice. Consequently, decreased LATS1 expression was significantly associated with the lymph node metastasis, poor prognosis and recurrence. Ectopic expression of LATS1 decreased GC cell proliferation and invasion in vitro and inhibited tumor growth and liver metastasis in vivo, but depletion of LATS1 expression restored the invasive phenotype. Further observation indicated that YAP pathway was required for LATS1-induced inhibition of cell growth and invasion, and LATS1 restrained nuclear transfer of YAP, downregulated YAP, PCNA, CTGF, MMP-2, MMP-9, Bcl-2 and CyclinD1 expression and upregulated p-YAP and Bax expression. Our findings suggest that LATS1 is a potential candidate tumor suppressor and inhibits the growth and metastasis of GC cells via downregulation of the YAP signaling.

Toosendanin inhibits growth and induces apoptosis in colorectal cancer cells through suppression of AKT/GSK-3ß/ß-catenin pathway.

AKT/GSK-3ß/ß-catenin signaling pathway plays an important role in the progression of colorectal cancer (CRC). Toosendanin (TSN) is a triterpenoid extracted from the bark or fruits of Melia toosendan Sieb et Zucc and possesses antitumour effects on various human cancer cells. However, its effect on CRC remains poorly understood. The present study investigated the effect of TSN on CRC SW480 cells and the AKT/GSK-3ß/ß-catenin signaling. Proliferation assay, flow cytometry and Hoechst 33342 nuclear staining demonstrated TSN dose-dependently inhibited cell viability and induced cell apoptosis as well as cell cycle arrest in S phase. Confocal laser scanning microscope showed ß-catenin transferred to the outside of the nucleus in TSN-treated cells. Quantitative real-time PCR and western blot analysis found that TSN effectively modulated molecules related to apoptosis and AKT/GSK-3ß/ß-catenin signaling. Moreover, TSN administration significantly inhibited CRC growth in a mouse tumor xenograft model. In conclusion, our findings indicate that TSN inhibits growth and induces apoptosis in CRC cells through suppression of AKT/GSK-3ß/ß-catenin pathway, suggesting that TSN may have potential for use in CRC treatment.