MiR-1290 targets CCNG2 to promote the metastasis of oral squamous cell carcinoma.

OBJECTIVE: MicroRNAs (miRNAs) have been demonstrated to be involved in the pathogenesis of various human cancers, including oral squamous cell carcinoma (OSCC). Here, we designed this study to explore the potential effect of miR-1290 on tumorigenesis of OSCC. PATIENTS AND METHODS: The expressions of miR-1290 and cyclin G2 (CCNG2) in OSCC were observed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Dual-Luciferase Reporter Assay was performed to confirm the relationship between miR-1290 and CCNG2. The functions of miR-1290 and CCNG2 were analyzed using transwell assay. The Western blot analysis was used to detect epithelial-mesenchymal transition (EMT). RESULTS: Upregulation of miR-1290 and downregulation of CCNG2 were identified in OSCC. And upregulation of miR-1290 was associated with clinicopathological characteristics and poor prognosis in OSCC patients. Moreover, the downregulation of miR-1290 inhibited cell metastasis and EMT in OSCC cells. Furthermore, CCNG2 was a direct target of miR-1290. Its expression was inversely regulated by miR-1290 in OSCC cells. At the same time, the suppressive effect of CCNG2 was observed in OSCC. Furthermore, overexpression of CCNG2 weakened the promoted effect of miR-1290 on cell metastasis in OSCC. CONCLUSIONS: MiR-1290 promoted cell metastasis and EMT, inhibiting CCNG2 expression in OSCC.

A novel DNA-binding motif in prostate tumor overexpressed-1 (PTOV1) required for the expression of ALDH1A1 and CCNG2 in cancer cells.

PTOV1 is a transcription and translation regulator and a promoter of cancer progression. Its overexpression in prostate cancer induces transcription of drug resistance and self-renewal genes, and docetaxel resistance. Here we studied PTOV1 ability to directly activate the transcription of ALDH1A1 and CCNG2 by binding to specific promoter sequences. Chromatin immunoprecipitation and electrophoretic mobility shift assays identified a DNA-binding motif inside the PTOV-A domain with similarities to known AT-hooks that specifically interacts with ALDH1A1 and CCNG2 promoters. Mutation of this AT-hook-like sequence significantly decreased the expression of ALDH1A1 and CCNG2 promoted by PTOV1. Immunohistochemistry revealed the association of PTOV1 with mitotic chromosomes in high grade prostate, colon, bladder, and breast carcinomas. Overexpression of PTOV1, ALDH1A1, and CCNG2 significantly correlated with poor prognosis in prostate carcinomas and with shorter relapse-free survival in colon carcinoma. The previously described interaction with translation complexes and its direct binding to ALDH1A1 and CCNG2 promoters found here reveal the PTOV1 capacity to modulate the expression of critical genes at multiple levels in aggressive cancers. Remarkably, the AT-hook motifs in PTOV1 open possibilities for selective targeting its nuclear and/or cytoplasmic activities.

Cyclin G2 suppresses Wnt/ß-catenin signaling and inhibits gastric cancer cell growth and migration through Dapper1.

BACKGROUND: Gastric cancer is one of the most common malignant tumors. Cyclin G2 has been shown to be associated with the development of multiple types of tumors, but its underlying mechanisms in gastric tumors is not well-understood. The aim of this study is to investigate the role and the underlying mechanisms of cyclin G2 on Wnt/ß-catenin signaling in gastric cancer. METHODS: Real-time PCR, immunohistochemistry and in silico assay were used to determine the expression of cyclin G2 in gastric cancer. TCGA datasets were used to evaluate the association between cyclin G2 expression and the prognostic landscape of gastric cancers. The effects of ectopic and endogenous cyclin G2 on the proliferation and migration of gastric cancer cells were assessed using the MTS assay, colony formation assay, cell cycle assay, wound healing assay and transwell assay. Moreover, a xenograft model and a metastasis model of nude mice was used to determine the influence of cyclin G2 on gastric tumor growth and migration in vivo. The effects of cyclin G2 expression on Wnt/ß-catenin signaling were explored using a TOPFlash luciferase reporter assay, and the molecular mechanisms involved were investigated using immunoblots assay, yeast two-hybrid screening, immunoprecipitation and Duolink in situ PLA. Ccng2-/- mice were generated to further confirm the inhibitory effect of cyclin G2 on Wnt/ß-catenin signaling in vivo. Furthermore, GSK-3ß inhibitors were utilized to explore the role of Wnt/ß-catenin signaling in the suppression effect of cyclin G2 on gastric cancer cell proliferation and migration. RESULTS: We found that cyclin G2 levels were decreased in gastric cancer tissues and were associated with tumor size, migration and poor differentiation status. Moreover, overexpression of cyclin G2 attenuated tumor growth and metastasis both in vitro and in vivo. Dpr1 was identified as a cyclin G2-interacting protein which was required for the cyclin G2-mediated inhibition of ß-catenin expression. Mechanically, cyclin G2 impacted the activity of CKI to phosphorylate Dpr1, which has been proved to be a protein that acts as a suppressor of Wnt/ß-catenin signaling when unphosphorylated. Furthermore, GSK-3ß inhibitors abolished the cyclin G2-induced suppression of cell proliferation and migration. CONCLUSIONS: This study demonstrates that cyclin G2 suppresses Wnt/ß-catenin signaling and inhibits gastric cancer cell growth and migration through Dapper1.

Morin inhibited lung cancer cells viability, growth, and migration by suppressing miR-135b and inducing its target CCNG2.

Lung cancer is one of the most severe threats with the highest mortality rate to humans in the world. Recently, morin has been reported to have anti-tumor properties observed in several types of cancers. However, its mechanism is still unclear. We assessed the influences of morin on cell viability, colony formation, and migration ability of A549 and employed microRNA array to identify the microRNAs affected by morin. We found that morin-treated A549 cells showed statistically decreased cell viability, colony formation, and migration rate when comparing with the dimethyl sulfoxide-treated cells. Microarray results showed that with the treatment of morin, the expression level of miR-135b significantly reduced compared the control group, suggesting that morin may exert its anti-cancer property by suppressing the expression of miR-135b. In addition, we found a potential binding site of miR-135b within 3' untranslated region of CCNG2-encoding cyclin homolog cyclin-G2. We evidenced that miR-135b directly targets CCNG2, which could be a potential biomarker of lung cancer prognosis. Morin exerts its anti-tumor function via downregulating the expression of miR-135b that directly targets and represses CCNG2.