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Aim: Circular RNAs (circRNAs) play important roles in the progression of human cancers. circRNA nuclear receptor interacting protein 1 (circNRIP1) has been reported to play as an oncogene in gastric cancer. However, the mechanism underlying circNRIP1 in gastric cancer progression is far from understood. Patients and Methods: Forty-five gastric cancer patients were recruited and overall survival of patients was analyzed. Gastric cancer cell lines MGC-803 and AGS cells were cultured for study in vitro. The expression levels of circNRIP1, microRNA (miR)-182 and rho-associated protein kinase 1 (ROCK1) were detected by quantitative real-time polymerase chain reaction or Western blot. Cell migration, invasion, cell cycle distribution and apoptosis were determined by transwell, flow cytometry and Western blot assays, respectively. The target association between miR-182 and circNRIP1 or ROCK1 was assessed by luciferase reporter assay and RNA immunoprecipitation. Results: circNRIP1 expression was enhanced in gastric cancer tissues and cells and high expression of circNRIP1 indicated poor survival of patients. Knockdown of circNRIP1 suppressed cell migration and invasion, arrested cell cycle at G0-G1 phase and promoted apoptosis in gastric cancer cells. miR-182 was a target of circNRIP1 and its deficiency reversed the effect of circNRIP1 silence on cell migration, invasion, cell cycle distribution and apoptosis in gastric cancer cells. Moreover, ROCK1 was validated as a target of miR-182 and competitively regulated by circNRIP1. Conclusion: Silence of circNRIP1 inhibited progression of gastric cancer by increasing miR-182 and decreasing ROCK1, providing a novel target for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) refer to a certain subpopulation within the tumor entity that is characterized by restricted cellular proliferation and multipotent differentiation potency. The existence of CSCs has been proven to contribute to the heterogeneity of malignancies, accounting for intensified tumorigenesis, treatment resistance, and metastatic spread. Dormancy was proposed as a reversible state of cancer cells that are temporarily arrested in the cell cycle, possessing several hallmarks that facilitate their survival within a devastating niche. This transient period is evoked to enter an actively proliferating state by multiple regulatory alterations, and one of the most significant and complex factors comes from local and systemic inflammatory reactions and immune components. Although CSCs and dormant cancer cells share several similarities, the clear relationship between these two concepts remains unclear. Thus, the detailed mechanism of immune cells interacting with CSCs and dormant cancer cells also warrants elucidation for prevention of cancer relapse and metastasis. In this review, we summarize recent findings and prospective studies on CSCs and cancer dormancy to conclude the relationship between these two concepts. Furthermore, we aim to outline the mechanism of immune components in interfering with CSCs and dormant cancer cells to provide a theoretical basis for the prevention of relapse and metastasis. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma is a major public health problem with the low 5-year survival rate (15%) among cancers. Aberrant alterations of meiotic genes, which have gained increased attention recently, might contribute to elevated tumor risks. However, systematic and comprehensive studies based on the relationship between meiotic genes and LUAD recurrence and treatment response are still lacking. In this manuscript, we first confirmed that the meiosis related prognostic model (MRPM) was strongly related to LUAD progression via LASSO-Cox regression analyses. Furthermore, we identified the role of PPP2R1A in LUAD, which showed more contributions to LUAD process compared with other meiotic genes in our prognostic model. Additionally, repression of PPP2R1A enhances cellular susceptibility to nelfinavir-induced apoptosis and pyroptosis. Collectively, our findings indicated that meiosis-related genes might be therapeutic targets in LUAD and provided crucial guidelines for LUAD clinical intervention. Highlights: Meiotic genes-related risk score (MRS) is a promising prediction feature with high reliability and accuracy for LUAD patients. PPP2R1A is overexpressed in LUAD and associated with malignancy. Nelfinavir inhibited cell viability and yields anti-tumor effects in LUAD cells. PPP2R1A silencing sensitizes cancer cells to nelfinavir induced cell apoptosis and pyroptosis. [ABSTRACT FROM AUTHOR]

Parameritannin A-2 (PA-2) is a natural product extracted from the stems of the plant Urceola huaitingii. Our previous studies have shown that PA-2 exhibits significant synergistic anticancer effects with doxorubicin (DOX) in HGC27 gastric cancer cell lines. Here we report that our isobolographic analysis confirms the synergistic cytotoxic effects of PA-2 and DOX in HGC27 cells. Flow cytometry and immunoblotting indicate that PA-2 enhances DOX-mediated apoptosis. Importantly, PA-2 enhances the intracellular accumulation of DOX in HGC27 cells. The combination of DOX and PA-2 remarkably increases the release of cytochrome C and the activation of caspase-3 and caspase-9, compared with DOX treatment alone. Moreover, PA-2 attenuates the DOX-induced activation of Akt, ERK1/2 and p38 signaling pathways, providing a molecular mechanism for the synergistic effects of DOX and PA-2 in the induction of apoptosis. In conclusion, our studies demonstrate that PA-2 and DOX synergistically induce mitochondria-dependent apoptosis as PA-2 inhibits the PI3K/Akt, ERK1/2 and p38 pathways in HGC27 cells. These findings suggest that the combination treatment with PA-2 and DOX may represent a potent therapy for gastric cancer. • PA-2 exhibits significant synergistic anticancer effects with DOX in HGC27 cells. • PA-2 enhances the intracellular accumulation of DOX in HGC27 cells. • PA-2 enhances DOX-mediated apoptosis. • PA-2 attenuates the DOX-induced activation of Akt, ERK1/2 and p38 signaling pathways. [ABSTRACT FROM AUTHOR]

A novel style of biomimetic nanovehicle is constructed for epigenetic inhibitor delivery, by virtue of the hybrid membrane to camouflage the epigenetic inhibitor loaded nanoparticles. Efficient epigenetic inhibition is achieved, leading to effective inhibition of cancer metastasis. Our work opens a new avenue for the treatment of metastatic lung cancer with biomimetic nanovehicle mediated epigenetic inhibition. [Display omitted] Histone deacetylase inhibitors (HDACIs), such as vorinostat (suberoylanilide hydroxamic acid, SAHA), has become a promising approach for the treatment of metastatic lung cancer. However, HDACIs usually showed a short circulation lifetime, low specificity, and low bioavailability, which limited their therapeutic effect in this field. We supposed that the use of biomimetic nanoparticles enabled to overcome the disadvantages of HDACIs, and improved the inhibition of metastatic lung cancer. SAHA was encapsulated into a pH-sensitive core constructed with Poly(lactic- co -glycolic acid) (PLAG) and 1,2-dioleoyloxy-3-(trimethylammonium) propane (DOTAP), followed by the camouflage with hybrid membranes derived from red blood cells and metastatic NCI-H1299 lung cancer cells (HRPDS). The physical and chemical properties were characterized with Transmission electron microscope (TEM), Size & Zeta potential analyzer. The cellular uptake was analyzed with Confocal laser scanning microscope (CLSM) and Flow cytometry (FACS). The biological effect analysis was performed with Western blotting (WB), RNA-Sequencing (RNA-Seq), and ChIP-Sequencing (ChIP-Seq). HRPDS exhibited enhanced circulation lifetime in vivo and homotypic targeting to metastatic cells in the metastatic foci, which induced significant suppression of lung cancer liver metastasis. Our work opens a new avenue for the treatment of metastatic lung cancer by epigenetic inhibition based on this style of biomimetic nanovehicle. [ABSTRACT FROM AUTHOR]

Background: Accumulating data suggested that circular RNAs (circRNAs) played important roles in the development of human cancer. However, the potential mechanism of circRNAs in ovarian cancer remains unclear. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the levels of circRNA itchy E3 ubiquitin protein ligase (circ-ITCH), microRNA-106a (miR-106a) and E-cadherin (CDH1). Cell Counting Kit-8 (CCK-8) and Transwell assay were carried out to measure cell proliferation and invasion. Glucose consumption, lactate production, and ATP level were assessed by the glucose, lactate, and ATP assay kits, respectively. Cell apoptosis was detected by Flow cytometry. The binding sites were predicted by StarBase v.2.0 or microT-CDS and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. CDH1 protein level was determined by western blot. The functional role of circ-ITCH was measured by xenograft tumor model in vivo. Results: Circ-ITCH was down-regulated in ovarian cancer and positively correlated with 5-year overall survival of patients with ovarian cancer. RNase R digestion assay confirmed that circ-ITCH was more stable than its linear mRNA form. Moreover, circ-ITCH was mainly distributed in the cytoplasm of ovarian cancer cells. Functionally, circ-ITCH overexpression hindered proliferation, invasion, glycolysis and promoted apoptosis of ovarian cancer cells. Besides, circ-ITCH overexpression inhibited ovarian cancer cell progression by targeting miR-106a. Additionally, CDH1 was a target of miR-106a, and the protein level of CDH1 was negatively regulated by miR-106a. Similarly, CDH1 knockdown recovered the inhibition effects of miR-106a inhibitor or circ-ITCH overexpression on the progression of ovarian cancer cells. Importantly, circ-ITCH up-regulated the protein level of CDH1 by sponging miR-106a in ovarian cancer cells. Circ-ITCH overexpression suppressed the growth of ovarian cancer cells in vivo. Conclusion: Circ-ITCH suppressed proliferation, invasion, glycolysis, and promoted apoptosis of ovarian cancer cells by modulating the miR-106a/CDH1 axis. [ABSTRACT FROM AUTHOR]