BackgroundThis study aimed to explore the effects of HMGA2 on cell proliferation and metastases in lung cancer and its underlying mechanism.Methods HMGA2 expression in lung cancer tissues and its association with overall survival were analyzed based on data from a public database. The roles of HMGA2 were validated via loss‐of‐function and gain‐of‐function experiments in vitro. HMGA2 regulation by microRNA‐195 (miR‐195) was validated by real time‐PCR, Western blotting, and luciferase reporter assays.Results HMGA2 was upregulated and associated with reduced overall survival in patients with lung adenocarcinoma. HMGA2 knockdown suppressed the proliferation and motility of H1299 cells, while HMGA2 ectopic expression in A549 cells increased cell proliferation and migration. HMGA2 affected cell apoptosis through caspase 3/9 and Bcl‐2, and regulated epithelial‐to‐mesenchymal transition by targeting Twist 1. Moreover, miR‐195 was found to directly target the 3′ untranslated region of HMGA2 messenger RNA and suppress its expression in lung cancer.ConclusionThis study demonstrated that HMGA2, regulated by miR‐195, played important roles in proliferation, metastases, and epithelial‐to‐mesenchymal transition in lung cancer. HMGA2 might serve as a biomarker and potential therapeutic target for lung cancer treatment.

Many studies have shown that long-noncoding RNA (lncRNA) is associated with cardiovascular disease, but its molecular mechanism is still unclear. In this study, we explored the role of lncRNA ANRIL in ox-LDL-induced phenotypic transition of human aortic smooth muscle cells (HASMC). The results of quantitative fluorescence PCR showed that the expression of ANRIL in patients with coronary atherosclerotic heart disease (CAD) was significantly higher than that in normal subjects. RNA-FISH detection showed that the ANRIL expression increased in HASMC treated by ox-LDL. Ox-LDL could upregulate the expression of ANRIL and ROS and promote the phenotypic transition of HASMC. After downregulation of ANRIL by siRNA, ROS level decreased and HASMC phenotypic transition alleviated. ANRIL could act as a molecular scaffold to promote the binding of WDR5 and HDAC3 to form WDR5 and HDAC3 complexes, they regulated target genes such as NOX1 expression by histone modification, upregulated ROS level and promote HASMC phenotype transition. Therefore, we found a new epigenetic regulatory mechanism for phenotype transition of VSMC, ANRIL was a treatment target of occlusive vascular diseases.

PurposeAccumulating evidence has shown that dysregulation of microRNA-191 (miR-191) is closely associated with tumorigenesis and progression in a wide range of cancers. This study aimed to explore the potential role of miR-191 in esophageal squamous cell carcinoma (ESCC).Materials and MethodsmiR-191 expression was assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony-forming, BrdU, and Transwell assays were conducted to observe the effect of miR-191 on ESCC proliferation and invasion. Luciferase reporter and western blot assays were taken to identify target genes of miR-191.ResultsmiR-191 was overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR-191 expression was significantly related to differentiation, depth of invasion, TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of ESCC prognosis. Both gain-of-function and loss-of-function experiments showed that miR-191 promoted ESCC cell proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a tumor suppressor, was predicted as a direct target of miR-191. Luciferase reporter and western blot assays proved that miR-191 reduced EGR1 expression by directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA enhanced ESCC cell growth and invasion.ConclusionOur findings provide specific biological roles of miR-191 in ESCC survival and progression. Targeting the novel miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC development.

This study investigated possible correlations between the presence of circulating tumor cells (CTCs) and the pathologic types and staging of non-small cell lung cancer (NSCLC) during the early postoperative period. Sixty-nine patients with NSCLC were enrolled in the study. Clinical staging was performed by postoperative pathological examination and imaging. Multiple mRNA in situ analyses targeting specifically expressed genes were carried out to identify the presence of CTCs. Correlations between age, sex, TNM stage and pathological types with the detection rate of CTCs were also established. The results showed the positivity rate of CTCs in patients >55 years was significantly higher than that of patients <55 years (94.74 vs. 70.97%, P<0.05). There was no significant difference in the positivity rate of CTCs between male and female patients (85.71 vs. 85.29%, P>0.05). The correlations between the detection rate of epithelial type or mixed type CTCs with tumor size, lymph node metastasis and distant metastasis TNM in patients with NSCLC were not significant (P>0.05). However, higher TNM stages correlated with higher detection rates of mesenchymal CTCs (P<0.05). There were also significant differences in the detection rates of CTCs amongst the three different pathologic types (adenocarcinoma, squamous cell and large cell carcinomas) (P<0.05). Based on our results, the detection of mesenchymal CTCs during the early postoperative period can help prognosticate the recurrence and metastasis of NSCLC, which is beneficial to the development of individualized treatment strategies.