Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) mediating chemotherapeutic drug effects and metastasis in pancreatic cancer (PC) are key reasons for the poor prognosis of this disease. lncRNA growth arrest-specific 5 (GAS5) is reported to be a tumor suppressor in multiple cancers. However, the functions of GAS5 and its related miRNAs in PC are poorly understood. This study explored the potential functions and mechanisms of GAS5 in PC gemcitabine resistance and metastasis. The results show that overexpression of GAS5 suppressed the proliferation, migration, gemcitabine resistance, stem cell-like properties, and epithelial-mesenchymal transition (EMT) of PC cells by directly binding to and suppressing miR-221 expression and enhancing suppressor of cytokine signaling 3 (SOCS3) expression. The effects of miR-221 overexpression on proliferation, migration, gemcitabine resistance, stem cell-like properties, and EMT inhibition were reversed by SOCS3 overexpression in PC cells. Additionally, GAS5 promoted gemcitabine-induced tumor growth and metastasis inhibition, as determined by Ki-67 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), bioluminescence imaging, and the detection of cell-like properties and EMT in vivo. Thus, lncRNA GAS5 functioned as a competing endogenous RNA for miR-221, and it suppressed cell growth, metastasis, and gemcitabine resistance in PC by regulating the miR-221/SOCS3 pathway mediating EMT and tumor stem cell self-renewal.

Background/Aims: Phosphoserine aminotransferase 1 (PSAT1) is over-expressed in many carcinoma tissues, however little is known regarding its expression and function in esophageal carcinogenesis. This study investigated the expression of PSAT1 in human esophageal squamous cell carcinoma (ESCC) tissues to determine the relationship between PSAT1 expression and clinicopathological factors. Methods: The expression of PSAT1 in 64 surgical resections from esophageal carcinogenesis patients was examined by quantitative RT-PCR and immunohistochemistry and the results were compared with clinicopathological factors. In vitro experiments were performed in ESCC cells overexpressing PSAT1 to measure cell viability and invasion. Tumor formation in vivowas examined by injection of tumor cells into immunocompromised mice subcutaneously. Results: PSAT1 expression was elevated in ESCC tissues compared to normal esophageal tissues. Increased PSAT1 expression was significantly associated with stage of disease, lymph node metastasis, distant metastasis and poor prognosis. In vitro, PSAT1 overexpression promoted ESCC cell proliferation and matrigel invasion. In vivo, injection of mice with ECSS cells overexpressing PSAT1 enhanced tumor formation. Western blot analysis revealed that PSAT1 upregulated the expression and/or activity of GSK3β/Snail. Conclusion: PSAT1 plays a crucial role in the development of ESCC and predicts poor survival. Therefore, PSAT1 may be a promising novel anticancer therapeutic target.

Pancreatic cancer is an aggressive malignancy with a high metastatic potential that results in a high mortality rate worldwide. Although macrophages have the potential to kill tumor cells and elicit immune responses against tumors, there is evidence that tumor-associated macrophages (TAMs) promote tumor progression and suppress T-cell responses. CC-chemokine ligand 20 (CCL20) and its unique receptor CC-chemokine receptor 6 (CCR6) are exploited by cancer cells for migration and metastasis and play important roles in the development and progression of cancer. Recent studies have shown that the expression of CCL20 is upregulated in pancreatic cancer; however, the mechanism of action of CCL20 remains to be fully elucidated. In this study, the aberrant expression of CCL20 in TAMs of pancreatic cancer tissue, including metastatic pancreatic cancer tissue, was detected. CCL20 expression was considerably higher in macrophages than in pancreatic cancer cell lines, particularly in interleukin-4-treated (M2) macrophages. Using Boyden chamber assays of pancreatic cancer cells, we found that CCL20 secreted by M2 macrophages promoted the migration, epithelial-mesenchymal transition, and invasion of pancreatic cancer cells. RNA interference results showed that CCR6 is a receptor for CCL20 in pancreatic cancer cells, mediating the increased invasive properties of these cells promoted by CCL20. Using a mouse model, we confirmed the roles of CCR6/CCL20 in promoting pancreatic cancer growth and liver metastasis in vivo Our findings provide insight into the important role of macrophage-secreted CCL20 in pancreatic cancer and implicate CCR6/CCL20 as potential therapeutic targets.

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Background Acute myocardial infarction (AMI) is considered one of the most prominent causes of death from cardiovascular disease worldwide. Knowledge of the molecular mechanisms underlying AMI remains limited. Accurate biomarkers are needed to predict the risk of AMI and would be beneficial for managing the incidence rate. The gold standard for the diagnosis of AMI, the cardiac troponin T (cTnT) assay, requires serial testing, and the timing of measurement with respect to symptoms affects the results. As attractive candidate diagnostic biomarkers in AMI, circulating microRNAs (miRNAs) are easily detectable, generally stable and tissue specific. Methods The Gene Expression Omnibus (GEO) database was used to compare miRNA expression between AMI and control samples, and the interactions between miRNAs and mRNAs were analysed for expression and function. Furthermore, a protein-protein interaction (PPI) network was constructed. The miRNAs identified in the bioinformatic analysis were verified by RT-qPCR in an H9C2 cell line. The miRNAs in plasma samples from patients with AMI (n = 11) and healthy controls (n = 11) were used to construct receiver operating characteristic (ROC) curves to evaluate the clinical prognostic value of the identified miRNAs. Results We identified eight novel miRNAs as potential candidate diagnostic biomarkers for patients with AMI. In addition, the predicted target genes provide insight into the molecular mechanisms underlying AMI.

Pancreatic ductal adenocarcinoma (PDAC) tumours exhibit a high level of heterogeneity which is associated with hypoxia and strong resistance to chemotherapy. The RNA splicing protein polypyrimidine tract‐binding protein 3 (PTBP3) regulates hypoxic gene expression by selectively binding to hypoxia‐regulated transcripts. We have investigated the role of PTBP3 in tumour development and chemotherapeutic resistance in human PDAC tissues and pancreatic cancer cells. In addition, we determined the sensitivity of cancer cells to gemcitabine with differential levels of PTBP3 and whether autophagy and hypoxia affect gemcitabine resistance in vitro. PTBP3 expression was higher in human pancreatic cancer than in paired adjacent tissues. PTBP3 overexpression promoted PDAC proliferation in vitro and tumour growth in vivo, whereas PTBP3 depletion had opposing effects. Hypoxia significantly increased the expression of PTBP3 in pancreatic cancer cells in vitro. Under hypoxic conditions, cells were more resistance to gemcitabine. Knockdown of PTBP3 results in decreased resistance to gemcitabine, which was attributed to attenuated autophagy. We propose that PTBP3 binds to multiple sites in the 3′‐UTR of ATG12 resulting in overexpression. PTBP3 increases cancer cell proliferation and autophagic flux in response to hypoxic stress, which contributes to gemcitabine resistance.

Perovskite-related materials with various dimensionalities have attracted sustained attention owing to their extraordinary electronic and optoelectronic properties, but it is still challenging in the synthesis of compounds with desired compositions and structures. Herein, a two-dimensional (2D) CsPb 2 I 5 perovskite has been synthesized by the conversion of CsPbI 3 at high-pressure and high-temperature (high P−T) conditions, which is quenchable at ambient conditions. In situ synchrotron X-ray diffraction shows that high-pressure monoclinic CsPbI 3 converts into tetragonal CsPb 2 I 5 and cubic CsI at 8.7 GPa upon heating from 644 to 666 K. Keeping the tetragonal structure stable, CsPb 2 I 5 exhibits tunable optical properties with the bandgap changing from ∼2.4 eV at ambient pressure to ∼1.4 eV at 36.9 GPa. Further experiments demonstrate similar structural evolution in the typical three-dimensional CsPbBr 3 perovskite into 2D CsPb 2 Br 5 at high P−T conditions, indicating that the conversion of CsPbX 3 (X = Br and I) into CsPb 2 X 5 is ubiquitous.

Circular RNA VANGL1 (circVANGL1) is generated from two exons of the Van Gogh‐like 1 (VANGL1) gene and serves as a tumor promoter by sponging certain microRNAs (miRNAs). However, the role of circVANGL1 in bladder cancer (BC) is still unclear. So, in order to investigate the role of circVANGL1 in BC, quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was employed to evaluate the circVANGL1 expression in tumor tissues from BC patients and in BC cell lines. Small interfering RNA against circVANGL1 was constructed and stably transfected into human bladder epithelium immortalized cells (SV‐HUC). Cell invasion and migration were detected in Transwell chambers, cell proliferation was determined by CCK8 assays, and tumorigenesis in nude mice was examined to assess the effect of circVANGL1 in BC. Subcellular localization of circVANGL1 was confirmed by fluorescence in situ hybridization. The interactive relationships among circVANGL1, miRNA, and relative proteins were confirmed by luciferase reporter assays. The results showed that circVANGL1 was upregulated in both BC tissues and cell lines. Silencing the expression of circVANGL1 suppressed cell invasion, migration, and proliferation during in vitro experiments. Mechanistically, we demonstrated that circVANGL1 upregulated the expression of miR‐1184 target gene insulin‐like growth factor‐binding protein 2 (IGFBP2) by sponging miR‐1184, which promoted the aggressive biological behaviors of BC. Taken together, our results indicate that circVANGL1 acts as a tumor promoter through the novel circVANGL1/miR‐1184/IGFBP2 axis. Hopefully, our study will provide new ideas for the clinical treatment of BC.