LINC01006 regulates the proliferation, migration and invasion of hepatocellular carcinoma cells through regulating miR-433-3p/CBX3 axis.

INTRODUCTION AND OBJECTIVES: LINC01006 has been verified to be correlated with several cancer types, whereas its biological function in hepatocellular carcinoma (HCC) is still elusive. This study aimed to elucidate the specific regulatory mechanism of LINC01006 in the tumorigenesis of HCC. MATERIALS AND METHODS: The expression of LINC01006, miR-433-3p and CBX3 in HCC tissues and cells was assessed by qRT-PCR or Western blot. MTT, wound-healing, and transwell assays were used to evaluate the effects of LINC01006 on cell viability, migration, and invasion in vitro. A mouse xenograft model was established for in vivo assays. The relations among LINC01006, miR-433-3p, and CBX3 were analyzed by MS2-RNA immunoprecipitation (RIP) and Dual-luciferase reporter (DLR) assays. RESULTS: The expression of LINC01006 was up-regulated in HCC tissues and cells. LINC01006 knockdown inhibited the viability, wound healing rate, and invasive cell number of HeP3B and SK-HeP-1 cells, and decreased the tumor volume and weight in a mouse xenograft model. MiR-433-3p was a target of LINC01006, and LINC01006 overexpression inhibited the viability, wound healing rate, and invasive cell number of HeP3B and SK-HeP-1 cells. In addition, CBX3 was a target of miR-433-3p, which was negatively regulated by miR-433-3p. CBX3 overexpression and miR-433-3p inhibition reversed the inhibiting effects of LINC01006 knockdown on the viability, migration, and invasion of HeP3B cells. CONCLUSIONS: Silencing of LINC01006 inhibited the viability, migration, and invasion of HCC cells through regulating miR-433-3p/CBX3 axis.

Genomic and Immunological Characterization of Pyroptosis in Lung Adenocarcinoma.

Pyroptosis is a programmed cell death that may either promote or hinder cancer growth under different circumstances. Pyroptosis-related genes (PRGs) could be a useful target for cancer therapy, and are uncommon in lung adenocarcinoma (LUAD). The expression profiles, mutation data and clinical information of LUAD patients were included in this study. A pyroptosis-related prognostic risk score (PPRS) model was constructed by performing Cox regression, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis to score LUAD patients. Somatic mutation and copy number variation (CNV), tumor immunity, and sensitivity to immunotherapy/chemotherapy were compared between different PPRS groups. Clinical parameters of LUAD were combined with PPRS to construct a decision tree and nomogram. Red module was highly positively correlated with pyroptosis. Seven genes (FCRLB, COTL1, GNG10, CASP4, DOK1, CCR2, and AQP8) were screened from the red module to construct a PPRS model. Significantly lower overall survival (OS), higher incidence of somatic mutation and CNV, elevated infiltration level of the immune cell together with increased probability of immune escape were observed in LUAD patients with higher PPRS, and were more sensitive to Cisplatin, Docetaxel, and Vinorelbine. We constructed a new PPRS model for patients with LUAD. The model might have clinical significance in the prediction of the prognosis of patients with LUAD and in the efficacy of chemotherapy and immunotherapy.

miR-21 Inhibitors Modulate Biological Functions of Gastric Cancer Cells via PTEN/PI3K/mTOR Pathway.

Gastric cancer is one of the most common malignancy in the world. microRNAs (miRNAs) are naturally occurring noncoding RNA that control gene expression by targeting messenger RNA (mRNA) for post-transcriptional repression or cleavage. This study focused on a specific miRNA, miR-21, which was overexpressed in gastric cancer and examined the effects of miR-21 inhibitor on biological functions of gastric cancer cells and its possible mechanism. Gastric cancer cells MKN74 were treated with miR-21 inhibitor, negative control, and blank control. Cell proliferation, colony formation, migration, and invasion were assessed. Real-time PCR and western blot were applied to examine the expression of phosphatase and tens in homolog deleted on chromosome ten (PTEN)/PI3K/mTOR pathway molecules. miR-21 inhibitor markedly suppressed proliferation, migration, invasion, and colony formation of gastric cancer cells. Anti-miR-21 treatment also reduced the expression ratio of B cell lymphoma 2 (Bcl-2)/Bax. Furthermore, miR-21 inhibition was associated with increased expression of PTEN, which in turn decreased the ratios of S235/236, S240/244, and p-AK/AKT in gastric cancer cells. Inhibiting miR-21 modulates biological functions of gastric cancer cells via PTEN/PI3K/mTOR pathway and miR-21 inhibitor may provide a novel therapeutic strategy for gastric cancer.

Silencing of glutaminase 1 resensitizes Taxol-resistant breast cancer cells to Taxol.

Taxol is a front­line chemotherapeutic agent for the treatment of patients with multiple types of tumor. However, resistance to Taxol remains one of the principal causes of cancer­associated mortality. Glutamine, which is metabolized via a glutaminase (GLS)­dependent process, termed glutaminolysis, is important in cell growth and metabolism. The present study reported a novel mechanism underlying Taxol resistance in breast cancer cells. By investigating the glutamine metabolism of breast cancer cells in response to treatment with Taxol in vitro, it was observed that Taxol induced the uptake of glutamine and the expression of GLS1. Notably, Taxol­resistant cancer cells exhibited upregulation in the metabolism of glutamine and expression of GLS1. In addition, overexpression of GLS1 rendered cancer cells resistant to Taxol, indicating that GLS1 may be the therapeutic target for overcoming Taxol resistance in clinical therapeutics. The results also demonstrated that knock­down of GLS1 using small interfering RNA, resensitized the Taxol­resistant breast cancer cells to Taxol.