Song Zhao

MiR-96 downregulates RECK to promote growth and motility of non-small cell lung cancer cells.

MicroRNAs play critical roles in the development and progression of non-small cell lung cancer (NSCLC). miR-96 acts as an oncogene in some malignancies, while its role in NSCLC is unclear. Here, we validated that miR-96 was significantly increased in both human NSCLC tissues and cell lines. Inhibition of miR-96 expression remarkably reduced cell proliferation, colony formation, migration, and invasion of NSCLC cells. Reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was identified as a target of miR-96 in NSCLC cells. In addition, the expression of RECK was found to be negatively correlated with the expression of miR-96 in NSCLC tissues. Our data suggest that miR-96 might promote the growth and motility of NSCLC cells partially by targeting RECK.

MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells

MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in human cancers. Increasing evidence shows that deregulation of miRNAs contributes to the development and progression of human non-small cell lung cancer (NSCLC). Here, we identified miR-186 as a tumor suppressor in NSCLC, which was decreased in NSCLC. Overexpression of miR-186 significantly inhibited proliferation, migration, and invasion of NSCLC cells. In addition, Rho-associated protein kinase 1 (ROCK1) was identified as a target of miR-186 in NSCLC cells. Restoration of ROCK1 remarkably reversed the tumor-suppressive effects of miR-186 on cell proliferation, migration, and invasion in NSCLC cells. Furthermore, ROCK1 was inversely correlated with miR-186 expression in NSCLC. Collectively, our data indicate that miR-186 functions as tumor suppressor in NSCLC by targeting ROCK1.

Esophageal cancer-selective expression of TRAIL mediated by MREs of miR-143 and miR-122

Esophageal cancer is one of the most common digestive system neoplasms and has a quite poor prognosis. TNF-related apoptosis-inducing ligand (TRAIL) induces the apoptosis in a wide range of cancer cells including esophageal cancers. However, TRAIL also activates apoptotic pathway in normal cells. To improve the specificity of TRAIL action, we employed the microRNA (miRNA) response elements (MREs) of miR-143 and miR-122 to restrict TRAIL expression mediated by an adenoviral vector (Ad-TRAIL-143-122) in esophageal cancer cells. The experiments showed that Ad-TRAIL-143-122 was able to highly express TRAIL in esophageal cancer cells, but not normal cells. The selective TRAIL expression also led to selective apoptosis in esophageal cancer cells. Ad-TRAIL-143-122 greatly reduced the viability of esophageal cancer cells without cytotoxicity to normal cells. In mice, Ad-TRAIL-143-122 suppressed the growth of esophageal cancer xenografts and protected liver from TRAIL-induced toxicity. In this study, we constructed a biologic vector that can express exogenous genes in a tumor-specific manner. This strategy can simultaneously treat cancer and prevent hepatoxicity and thus may be a promising way for esophageal cancer treatment.

Inhibition of non-small-cell lung cancer cell proliferation by Pbx1

Lung cancer is one of the most deadly human cancers and continues to be a major unsolved health problem worldwide. Here, we evaluate the function of Pbx1 in the proliferation of non-small-cell lung cancer (NSCLC). In contrast with its known proliferative function, we found that Pbx1 inhibits the proliferation of lung cancer cells. In particular, Pbx1-specific RNA interference resulted in increased proliferation in lung cancer cells. In addition, histone H3 phosphorylation was also increased following inhibition of Pbx1 expression. In contrast, Pbx1 overexpression repressed the proliferation of lung cancer cells and inhibited DNA synthesis. Collectively, our data indicate that Pbx1 inhibits proliferation in lung cancer cells, suggesting a complex role for Pbx1 in modulating the proliferation of cancer cells and making this protein a potential new target for lung cancer therapy.

Prognostic and clinicopathological significance of Beclin-1 in non-small-cell lung cancer: a meta-analysis

Background Autophagy plays a key role in the development of non-small-cell lung cancer (NSCLC). Beclin-1 is essential for the initiation and regulation of autophagy. Accumulated studies have investigated the prognostic role of Beclin-1 in NSCLC, but conclusions remain controversial. Therefore, we conducted this meta-analysis to assess the potential significance of Beclin-1 in NSCLC. Materials and methods PubMed and Embase databases were searched for eligible studies published before December 31, 2017. Odds ratio (OR) was pooled to evaluate the clinicopathological significance of Beclin-1 in NSCLC. Hazard ratio (HR) was adopted to assess the association of Beclin-1 with overall survival (OS). Results Eight studies involving 1,159 patients were included in this meta-analysis. The pooled results showed that high Beclin-1 expression was significantly correlated with earlier tumor grade (OR=0.54, 95% CI: 0.36–0.81, P=0.003), less nodal involvement (OR=0.56, 95% CI: 0.37–0.86, P=0.007), earlier TNM stage (OR=0.62, 95% CI: 0.43–0.89, P=0.010), smaller tumor size (OR=0.54, 95% CI: 0.36–0.81, P=0.003), better differentiation (OR=0.48, 95% CI: 0.36–0.64, P<0.001), and less recurrence (OR=0.24, 95% CI: 0.14–0.41, P<0.001). Moreover, high level of Beclin-1 was significantly associated with better OS in NSCLC (HR=0.41, 95% CI: 0.26–0.64, P<0.001). Conclusion Our meta-analysis suggests that high Beclin-1 expression predicts a better clinicopathological status and a better prognosis in NSCLC. Beclin-1 might act as a promising prognostic biomarker for NSCLC.

Original Research: miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells

Increasing evidence suggests that miR-194 is down-regulated in esophageal squamous cell carcinoma tumor tissue. However, the role and underlying mechanism of miR-194 in esophageal squamous cell carcinoma have not been well defined. We used DIANA, TargetScan and miRanda to perform target prediction analysis and found KDM5B is a potential target of miR-194. Based on these findings, we speculated that miR-194 might play a role in esophageal squamous cell carcinoma development and progression by regulation the expression of KDM5B. We detected the expression of miR-194 and KDM5B by quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot assays, respectively, and found down-regulation of miR-194 and up-regulation of KDM5B existed in esophageal squamous cell carcinoma cell lines. By detecting proliferation, invasion and apoptosis of TE6 and TE14 cells transfected with miR-194 mimics or mimic control, miR-194 was found to inhibit proliferation and invasion and promote apoptosis of esophageal squamous cell carcinoma cells. miR-194 was further verified to regulate proliferation, apoptosis and invasion of esophageal squamous cell carcinoma cells by directly targeting KDM5B. Furthermore, animal studies were performed and showed that overexpression of miR-194 inhibited the growth of esophageal squamous cell carcinoma tumors in vivo. These results confirmed our speculation that miR-194 targets KDM5B to inhibit esophageal squamous cell carcinoma development and progression. These findings offer new clues for esophageal squamous cell carcinoma development and progression and novel potential therapeutic targets for esophageal squamous cell carcinoma.