CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer.

Rationale: Resistance to androgen-deprivation therapy (ADT) associated with metastatic progression remains a challenging clinical task in prostate cancer (PCa) treatment. Current targeted therapies for castration-resistant prostate cancer (CRPC) are not durable. The exact molecular mechanisms mediating resistance to castration therapy that lead to CRPC progression remain obscure. Methods: The expression of MYB proto-oncogene like 2 (MYBL2) was evaluated in PCa samples. The effect of MYBL2 on the response to ADT was determined by in vitro and in vivo experiments. The survival of patients with PCa was analyzed using clinical specimens (n = 132) and data from The Cancer Genome Atlas (n = 450). The mechanistic model of MYBL2 in regulating gene expression was further detected by subcellular fractionation, western blotting, quantitative real-time PCR, chromatin immunoprecipitation, and luciferase reporter assays. Results: MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells. Finally, high MYBL2 levels were positively associated with TNM stage, total PSA level, and Gleason score and predicted a higher risk of metastatic relapse and poor prognosis in patients with PCa. Conclusions: Our results reveal a novel molecular mechanism conferring resistance to ADT and provide a strong rationale for potential therapeutic strategies against CRPC.

MicroRNA-45 (miR-145) has been demonstrated to be downregulated in various cancer types including colorectal cancer (CRC). However, the function of miR‑145 in CRC has not been clearly elucidated. In this study, we examined miR-145 expression by quantitative real‑time PCR (qRT‑PCR) in CRC cell lines as well as tumors and corresponding normal mucosa, and the results were correlated to the clinicopathological parameters. In addition, using computational algorithms we investigated putative miR‑145 targets. The role of miR‑145 was further examined in studies in vitro. In our study miR‑145 was significantly decreased in CRC tissues and cell lines compared with non‑cancerous colorectal mucosa, especially lymph node or distance metastasis cases. Based on computational algorithms, we assumed that ERG was directly modulated by miR‑145 in colorectal cancer cells. For the first time, we demonstrated that ERG was highly expressed in CRC tissues compared with normal ones by qRT‑PCR. The inverse correlation between the expression of miR‑145 and ERG was observed in CRC tissues. Dual‑Luciferase assays demonstrated the direct interaction between miR‑145 and 3'‑UTR of ERG mRNA. Ectopic expression of miR‑145 suppressed the proliferation and invasion ability of colorectal cancer cells, while ERG knockdown partially restored the tumor suppressive effect of miR‑145. These results suggested that miR‑145 might act as a tumor suppressor during the process of CRC malignant transformation by interacting with ERG.

Colorectal cancer represents a lethal disease that has raised concern and has attracted significant attention. Adenocarcinoma is the most common type of colorectal cancer (CRC). MicroRNAs are thought to be potential biomarkers of CRC. Many researchers have focused on the expression pattern of miRNAs in CRC. However, previous studies did not pay particular attention to the effects of the degree of differentiation of the cancer with respect to the miRNA expression profile. First, this study compared the expression level of 1547 miRNAs by qRT-PCR in Colorectal adenocarcinoma tissues to that in paired normal tissues. In all, 93 miRNAs were identified that were significantly dysregulated in Colorectal adenocarcinoma relative to normal tissues (P<0.05). Then, we analyzed their potential as cancer biomarkers by ROC analysis, and the result revealed that three miRNAs with high sensitivity and specificity are suitable as biomarkers for the diagnosis of CRC (the value of the AUC was greater than 0.7). Interestingly, previous reports of 23 of these miRNAs have been scarce. Furthermore, we wanted to analyze the difference between well- and moderately differentiated cancers, and as expected, 58 miRNAs showed significant dysregulation. Importantly, 32 miRNAs were able to not only distinguish cancer tissues from normal tissues, but they were also able to identify well- and moderately differentiated cancers. In conclusion, the degree of differentiation has an important influence on the miRNA expression pattern. To avoid misdiagnoses and missed diagnoses, tumors of different degrees of differentiation should be treated differently when miRNAs are used as cancer biomarkers.

HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. However, its clinical significance and biological role in colorectal cancer (CRC) remain unclear. In the present study, the expression of HES6 was significantly upregulated in CRC cell lines and CRC tissues at both the mRNA and protein levels. The present study also reported high expression of HES6 in 138/213 (64.8%) paraffin-embedded archived CRC specimens. HES6 expression was significantly correlated with T classification (P<0.001), N classification (P=0.020), and distant metastasis (P<0.001). Patients with higher HES6 expression levels exhibited a reduced overall survival (P<0.001). In addition, a multivariate analysis revealed that the expression of HES6 may be a novel prognostic marker for the survival of patients with CRC. Furthermore, the present study demonstrated that ectopic expression of HES6 enhanced the migration and invasive abilities of CRC cells. These abilities were significantly inhibited upon knockdown of endogenous HES6 expression by specific short hairpin RNAs. Additionally, the present study reported that the effects of HES6 on metastasis may be associated with the activation of the Wnt/β-catenin signaling pathway. Collectively, the findings of the present study revealed that overexpression of HES6 played a key role in the progression of CRC, leading to a poor prognosis and clinical outcome.