Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in adults. Previous studies in our laboratory found that long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated in HCC cells, which could affect the metastasis and invasion of HCC. However, the underlying mechanism remains unknown. Herein, we studied the interaction between MALAT1 and miR-140 on the regulation of angiogenesis and immunosuppressive properties. We revealed that the expression of MALAT1 and VEGF-A was significantly increased in HCC cells. Knockdown of MALAT1 in HCC cells suppressed the production of VEGF-A, impaired the angiogenesis of HUVECs, and facilitated the polarization of macrophage toward the M1 subset. Mechanistically, the interaction between MALAT1 and miR-140 or between miR-140 and VEGF-A was confirmed by multiple assays. Besides, a negative correlation between MALAT1 and miR-140 was found in HCC tissues. Furthermore, miR-140 inhibition significantly increased VEGF-A expression, promoted angiogenesis of HUVECs, and redirected the polarization of macrophages toward the M2 subset. In addition, in vivo studies also verified the regulatory network of the MALAT1/miR-140 axis on VEGF-A in HCC progression. In summary, this study revealed the mechanism that MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in the future.

Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis-associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma.

Purpose: The purpose of this study was to determine the risk factors associated with pneumonia, acute respiratory distress syndrome (ARDS), and clinical outcome among patients with novel coronavirus disease 2019 (COVID-19). Methods: This was a cross-sectional multicenter clinical study. A total of 95 patients infected with COVID-19 were enrolled. The COVID-19 diagnostic standard was polymerase chain reaction detection of target genes of 2019 novel coronavirus (2019-nCoV). Clinical, laboratory, and radiologic results, as well as treatment outcome data, were obtained. ARDS was defined as an oxygenation index (arterial partial pressure of oxygen/fraction of inspired oxygen) 300 mm Hg. Findings: Multivariate analysis showed that older age (odds ratio [OR], 1.078; p ¼ 0.008) and high body mass index (OR, 1.327; p ¼ 0.024) were independent risk factors associated with patients with pneumonia. For patients with ARDS, multivariate analysis showed that only high systolic blood pressure (OR, 1.046; p ¼ 0.025) and high lactate dehydrogenase level (OR, 1.010; p ¼ 0.021) were independent risk factors associated with ARDS. A total of 70 patients underwent CT imaging repeatedly after treatment. Patients were divided in a disease exacerbation group (n ¼ 19) and a disease relief group (n ¼ 51). High body mass index (OR, 1.285; p ¼ 0.017) and tobacco smoking (OR, 16.13; p ¼ 0.032) were independent risk factors associated with disease exacerbation after treatment. Implications: These study results help in the risk stratification of patients with 2019-nCoV infection. Patients with risk factors should be given timely intervention to avoid disease progression. (Clin Ther.