Effectively targeting cancer stem cells to treat cancer has great therapeutic prospects. However, the effect of microRNA miR-17/MKL-1 on gastric cancer stem cells has not been studied yet. This study preliminarily explored the mechanism of miR-17/MKL-1 in gastric cancer stem cells. Many previous reports have indicated that microRNA and EMT regulated cancer stem cell characteristics, and miR-17 and MKL-1 were involved as a critical gene in migration and invasion in the EMT pathway. Through RT-PCR, Western Blot, flow cytometry, immunofluorescence, sphere formation xenograft tumor assays and drug resistance, the role of miR-17-5p and MKL-1 on promoting stem cell-like properties of gastric cancer were verified in vivo and vitro. Next, MKL-1 targets CD44, EpCAM, and miR -17-5p promoter verified by luciferase assay and ChIP. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. It is found that MKL-1 promotes expression by targeting miR-17, CD44 and EpCAM promoters. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. These findings reveal new regulatory signaling pathways for gastric cancer stem cells, thus it give new insights on potential early diagnosis and/or molecular therapy for gastric cancer.Circular RNA (circRNA) is a type of covalently closed and endogenous non-coding RNA (ncRNA) with tissue- and cell-specific expression patterns generated by a non-canonical splicing event. Previous reports have indicated that circRNAs exert their functions in different ways, thereby participating in various pathophysiological processes. N6 -methyladenosine (m6A) methylation occurs in the N 6-position, which is the most abundant and conserved internal transcriptional modification in eukaryotes, including mRNA and ncRNAs. Accumulating evidences confirm that m6A modification also exists in the circRNA and greatly affects the biological functions of circRNA. Their dysregulated expression can be a cause of various pathophysiological processes, such as spermatogenesis, myoblast differentiation, cancer, cardiovascular disease, mental illness and so on. Understanding the role of m6A-modified circRNAs in pathophysiological processes may contribute to better understanding the physiological mechanisms and develop new biomarkers. This review summarizes the regulatory mechanism of m6A modification on circRNA metabolism and the role of m6A-modified circRNAs in pathophysiological processes. This article may pave the way for a better understanding of the role of epigenetically modified circRNAs in pathophysiological process.Heme oxygenase 1 (HO-1), also known as heat shock protein 32 (HSP32), is a stress-inducible enzyme. In the past, it was believed to participate in maintaining cell homeostasis, reducing oxidative stress damage and exerting anti-apoptotic effects. When exposed to noxious stimulation, the expression of HO-1 in the body will increase, antagonizing these oxidative stresses and protecting our bodies. Recently, many studies showed that HO-1 was also highly-expressed in multiple gynecological cancers (such as ovarian cancer, cervical cancer and endometrial cancer), suggesting that it should be closely related to cell proliferation, metastasis, immune regulation and angiogenesis as an oncogene. This review summarizes the different effects of HO-1 under normal and diseased conditions with a brief discussion of its implications on the diagnosis and treatment of gynecological cancers, aiming to provide a new clue for prevention and treatment of diseases.Leflunomide (Lef) is an agent used in autoimmune disorders that interferes with DNA synthesis. De Novo pyrimidine synthesis is a mechanism of Gemcitabine (Gem) resistance in pancreatic cancer. This study aims to assess the efficacy and changes in the tumor microenvironment of Lef monotherapy and in combination with Gem, in a syngeneic mouse model of pancreatic cancer. Methods MTS proliferation assays were conducted to assess growth inhibition by Gem (0-20 nM), Lef (0-40 uM) and Gem+Lef in KPC (KrasLSL.G12D/+;p53R172H/+; PdxCretg/+) cells in vitro. An in vivo heterotopic KPC model was used and cohorts were treated with PBS (control), Gem (75 mg/kg/q3d), Lef (40 mg/kg/d), or Gem+Lef. At d28 post-treatment, tumor burden, proliferation index (Ki67), and vascularity (CD31) were measured. Changes in the frequency of peripheral and intratumoral immune cell subsets were evaluated via FACS. Liquid chromatography-mass spectrometry was used for metabolomics profiling. Results Lef inhibits KPC cell growth and synergizes with Gem in vitro (P less then 0.05; Combination Index 0.44 ( less then 1 indicates synergy). In vivo, Lef alone and in combination with Gem delays KPC tumor progression (P less then 0.001). CTLA-4+T cells are also significantly decreased in tumors treated with Lef, Gem or in combination (Gem+Lef) compared to controls (P less then 0.05). Combination therapy also decreased the Ki67 and vascularity (P less then 0.01). Leflunomide inhibits de novo pyrimidine synthesis both in vitro (p less then 0.0001) and in vivo (p less then 0.05). selleck chemicals llc Conclusions In this study, we demonstrated that Gem+Lef inhibits pancreatic cancer growth, decrease T cell exhaustion, vascularity and as proof of principle inhibits de novo pyrimidine synthesis. Further characterization of changes in adaptive immunity are necessary to characterize the mechanism of tumor growth inhibition and facilitate translation to a clinical trial.Overexpression of pyrroline-5-carboxylate reductase 1 (PYCR1) has been associated with the development of certain cancers; however, no studies have specifically examined the role of PYCR1 in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas expression array and meta-analysis conducted using the Gene Expression Omnibus database, we determined that PYCR1 was upregulated in HCC compared to adjacent nontumor tissues (P less then 0.05). These data were verified using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry analysis. Additionally, patients with low PYCR1 expression showed a higher overall survival rate than patients with high PYCR1 expression. Furthermore, PYCR1 overexpression was associated with the female sex, higher levels of alpha-fetoprotein, advanced clinical stages (III and IV), and a younger age ( less then 45 years old). Silencing of PYCR1 inhibited cell proliferation, invasive migration, epithelial-mesenchymal transition, and metastatic properties in HCC in vitro and in vivo.