circ_0008797 attenuates non-small cell lung cancer proliferation, metastasis, and aerobic glycolysis by sponging miR-301a-3p/SOCS2.

PURPOSE: This paper firstly reported the exact function of circ_0008797 on non-small cell lung cancer (NSCLC) progression. METHODS: NSCLC tissues/matched normal tissues were harvested from 88 NSCLC patients. RNA fluorescence in situ hybridization experiment was applied to detect circ_0008797 localization in NSCLC cells. circ_0008797 effect on NSCLC cells proliferation, migration, invasion, glucolysis, and apoptosis was researched by cell counting kit-8 assay, 5-ethynyl-2'deoxyuridine assay, Transwell experiment, glycolysis assay, and TUNEL assay. Dual luciferase reporter gene assay, RNA pull-down assay and RNA immunoprecipitation assay were used to verify the binding relationship between two genes. In vivo tumorigenesis and lung metastasis was performed using nude mice. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and western blot were applied for genes expression detection. Hematoxylin and eosin staining was performed on lung tissues. RESULTS: circ_0008797 was low expressed in NSCLC tissues and cell lines, associating with poor outcome (p <.05). circ_0008797 was mainly expressed in NSCLC cells cytoplasm. circ_0008797 inhibited proliferation, migration, invasion, and glycolysis, but enhanced apoptosis of NSCLC cells (p <.05). circ_0008797 attenuated malignant phenotype of NSCLC cells by sponging miR-301a-3p. circ_0008797 facilitated SOCS2 expression by sponging miR-301a-3p. SOCS2 knockdown partially reversed the inhibitory effect of miR-301a-3p inhibition on NSCLC cells malignant phenotype (p <.05). circ_0008797 attenuated NSCLC prolifearion and metastasis in vivo (p <.05). CONCLUSION: circ_0008797 attenuates NSCLC proliferation, metastasis and aerobic glycolysis by sponging miR-301a-3p/SOCS2.

A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel.

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

YY1/circCTNNB1/miR-186-5p/YY1 positive loop aggravates lung cancer progression through the Wnt pathway.

Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the functions and related regulatory mechanisms of circCTNNB1 in lung cancer remain largely indistinct. The mRNA and protein expression levels were examined through real-time polymerase chain reaction (RT-qPCR) and western blot. The cell proliferation was tested through CCK-8 assay. The cell migration and invasion were confirmed through Transwell assays. The cell senescence was evaluated through SA-ß-gal assay. The binding ability between miR-186-5p and circCTNNB1 (or YY1) was verified through luciferase reporter and RIP assays. In this study, the higher expression of circCTNNB1 was discovered in lung cancer tissues and cell lines and resulted in poor prognosis. In addition, circCTNNB1 facilitated lung cancer cell proliferation, migration, invasion, and suppressed cell senescence. Knockdown of circCTNNB1 retarded the Wnt pathway. Mechanism-related experiments revealed that circCTNNB1 combined with miR-186-5p to target YY1. Through rescue assays, YY1 overexpression could rescue decreased cell proliferation, migration, invasion, increased cell senescence, and retarded Wnt pathway mediated by circCTNNB1 suppression. Furthermore, YY1 acts as a transcription factor that can transcriptionally activate circCTNNB1 to form YY1/circCTNNB1/miR-186-5p/YY1 positive loop. Through in vivo assays, circCTNNB1 accelerated tumour growth in vivo. All findings revealed that a positive loop YY1/circCTNNB1/miR-186-5p/YY1 aggravated lung cancer progression by modulating the Wnt pathway.

Sodium valproate induces cell senescence in human hepatocarcinoma cells.

Hepatocarcinogenesis is associated with epigenetic changes, including histone deacetylases (HDACs). Epigenetic modulation by HDAC inhibition is a potentially valuable approach for hepatocellular carcinoma treatment. In present study, we evaluated the anticancer effects of sodium valproate (SVP), a known HDAC inhibitor, in human hepatocarcinoma cells. The results showed SVP inhibited the proliferation of Bel-7402 cells in a dose-dependent manner. Low dose SVP treatment caused a large and flat morphology change, positive SA-ß-gal staining, and G0/G1 phase cell cycle arrest in human hepatocarcinoma cells. Low dose SVP treatment also increased acetylation of histone H3 and H4 on p21 promoter, accompanied by up-regulation of p21 and down-regulation of RB phosphorylation. These observations suggested that a low dose of SVP could induce cell senescence in hepatocarcinoma cells, which might correlate with hyperacetylation of histone H3 and H4, up-regulation of p21, and inhibition of RB phosphorylation. Since the effective concentration inducing cell senescence in hepatocarcinoma cells is clinically available, whether a clinical dose of SVP could induce cell senescence in clinical hepatocarcinoma is worthy of further study.

Screening biomarkers for predicting the efficacy of immunotherapy in patients with PD-L1 overexpression.

PURPOSE: Immunotherapy plays an important role in non-small cell lung cancer (NSCLC); in particular, immune checkpoint inhibitors (ICIs) therapy has good therapeutic effects in PD-L1-positive patients. This study aims to screen NSCLC patients with PD-L1-positive expression and select effective biomarkers for ICI immunotherapy. METHODS: Collected tumor samples from the Affiliated Cancer Hospital of Xinjiang Medical University and 117 patients with stage III-IV NSCLC were included in the study. All patients were on first- or second-line therapy and not on targeted therapy. Based on the molecular profiles and clinical features, we screened biomarkers for predicting the efficacy of immunotherapy in patients with PD-L1 overexpression. RESULTS: 117 NSCLC patients receiving ICIs immunotherapy were enrolled. First, we found that immunotherapy was more effective in patients with positive PD-L1 expression. Second, we found that ROS1 gene mutations, KRAS gene mutations, tumor stage, and the endocrine system diseases history are independent prognostic factors for PD-L1 positive patients. Then we combined independent risk factors and constructed a new Nomogram to predict the therapeutic efficacy of ICIs immunotherapy in PD-L1 positive patients. The Nomogram integrates these factors into a prediction model, and the predicted C-statistic of 3 months, 6 months and 12 months are 0.85, 0.84 and 0.85, which represents the high predictive accuracy of the model. CONCLUSIONS: We have established a model that can predict the efficacy of ICIs immunotherapy in PD-L1 positive patients. The model consists of ROS1 gene mutations, KRAS gene mutations, tumor staging, and endocrine system disease history, and has good predictive ability.

Effect of Hysteroscopic Polypectomy Combined with Mirena Placement on Postoperative Adverse Reactions and Recurrence Rate of Endometrial Polyps: Based on a Large-Sample, Single-Center, Retrospective Cohort Study.

Objective: To investigate the effect of hysteroscopy surgery combined with Mirena on postoperative adverse reactions and recurrence rate of endometrial polyps (EP). Methods: A total of 312 patients who underwent hysteroscopic polypectomy of EP in our hospital from June 2017 to November 2020 were enrolled retrospectively. Among them, 42 patients did not take any treatment after the operation (control group), 156 patients were treated with levonorgestrel intrauterine birth control system (Mirena group), and 114 patients were treated with oral spironolone ethinylestradiol tablets (oral group). The clinical data of 312 patients were recorded and followed up regularly. All patients were followed up through an outpatient clinic or telephone to 12 months after the operation. The patients' age, disease course, number of pregnancies, clinical manifestations, endometrial thickness before the operation, duration of operation, amount of bleeding during the operation, and number and size of polyps were analyzed. The recurrence and postoperative side effects of EP in the three groups were followed up within 12 months after the operation. Results: There was no significant difference in endometrial thickness among the three groups before treatment (P > 0.05). After 3 months, 6 months, and 12 months of treatment, the endometrial thickness of the three groups decreased, while the decrease in the Mirena group and the oral group was better compared to the control (P < 0.05). The decrease in the Mirena group was better than that in the oral group (P < 0.05). There was no significant difference in hemoglobin levels among the three groups before treatment (P > 0.05). After 3, 6, and 12 months of treatment, the hemoglobin levels of the three groups increased to varying degrees, while the levels of the Mirena group and oral group were better compared to the control (P < 0.05). Three months after the operation, the improvement of clinical symptoms was similar in the three groups, and there was no significant difference among the three groups (P > 0.05). At 6 and 12 months after the operation, the improvement of clinical symptoms in the oral group and Mirena group was better compared to the control group (P < 0.05), but there was no significant difference between the oral group and Mirena group (P > 0.05). After the operation, some patients had complications such as lower abdominal pain, breast distension pain, irregular vaginal bleeding, and abnormal liver function. There was no significant difference in the number of complications among the three groups (P > 0.05). During the follow-up to 12 months after the operation, the recurrence rate in the oral group and Mirena group was lower compared to the control (P < 0.05), and the recurrence rate in the Mirena group was lower than that in the oral group (P < 0.05). Conclusion: Placing Mirena immediately after hysteroscopic polypectomy of EP can reduce the recurrence rate of endometrial polyps, increase the level of hemoglobin, and reduce the thickness of the endometrium, which can be employed and popularized according to the condition of patients in clinical work.

A Bibliometric Analysis of the Literature on Irisin from 2012-2021.

Irisin is a hormone-like molecule mainly released by skeletal muscles in response to exercise, which is proposed to induce the 'browning' of white adipose tissue. Since its identification, irisin was reported to be closely associated with many metabolic diseases, including type 2 diabetes mellitus (T2DM), obesity, cardiovascular disease (CVD), and metabolic bone diseases. In recent years, irisin has attracted increasing research interest, and numerous studies have been published in this field. Thus, it is essential to identify the current research status of irisin and measure research hotspots and possible future trends. In this study, by utilizing two visualization software named CiteSpace and VOSviewer, we analyzed 1510 Web of Science publications on irisin published from 2012 to 2021. Our results show that the number of irisin-related articles published annually has increased significantly. China participates in the most studies, followed by the United States and Turkey. Firat University, Harvard University, and Shandong University are three major institutions with larger numbers of publications. The analysis of keywords co-occurrence indicates that insulin resistance, inflammation, and circulating irisin levels in serum are the research hotspots. Apoptosis, BDNF, and osteoporosis will likely become the focus of future research related to irisin. Overall, this study may provide helpful insights for researchers to understand the current research situation and identify the potential frontiers of irisin.

Level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low regulatory T cells in vulvar lichen sclerosus.

This study is to investigate the pathogenesis of vulvar lichen sclerosus (VLS) by analyzing the level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low Regulatory T cells (Tregs). This study enrolled 15 VLS patients and 25 controls. Lesional and extralesional vulvar skin tissues, normal vulvar skin tissues and peripheral blood were collected. Compared with the control group, Foxp3 protein in the lesional and extralesional skin of VLS group was significantly reduced. The levels of DNMT1 and DNMT3b proteins in lesional skin of VLS group were significantly increased. There was no difference in the total methylation rates of the promoter region of the Foxp3 gene. The methylation rates of CpG1, CpG4, CpG9, and CpG10 were significantly higher in lesional skin of VLS group than in control group. There was no correlation between the total methylation rates of 10 CpG sites and the level of Foxp3 and DNMT1 proteins; there was a positive correlation between Foxp3 and DNMT1 protein in lesional skin of VLS group (r = 0.675, p < 0.05), and a negative correlation (r = -0.665, p < 0.05) in extralesional skin of VLS group. However, there was no correlation of Foxp3 with DNMT3b. The number of CD4 + CD25 + CD127low Tregs VLS decreased significantly. The expression of Foxp3 protein and the quantity of CD4 + CD25 + CD127low Tregs in patients with VLS decreased, which may cause local or systemic abnormal immunosuppression of Tregs, leading to the occurrence of VLS. This may be related with methylation or DNMT1, which needs further verification.

Knockdown of Long Non-Coding RNA HOTAIR Suppresses Cisplatin Resistance, Cell Proliferation, Migration and Invasion of DDP-Resistant NSCLC Cells by Targeting miR-149-5p/Doublecortin-Like Kinase 1 Axis.

BACKGROUND: Long non-coding RNA (lncRNA) HOTAIR has been reported to be associated with cisplatin (DDP) resistance in different human cancers including non-small cell lung cancer (NSCLC). However, the mechanism of HOTAIR in cisplatin resistance of NSCLC remains largely undefined. MATERIALS AND METHODS: Expression of HOTAIR, miR-149-5p and doublecortin-like kinase 1 (DCLK1) was detected using real-time quantitative PCR (RT-qPCR) and Western blotting. Cisplatin resistance was determined with cell counting kit (CCK)-8 assay and transwell assays in vitro, and xenograft tumor models in vivo. The target binding between miR-149-5p and either HOTAIR or DCLK1 was predicted on Diana Tools website, and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. RESULTS: Expression of HOTAIR was upregulated in DDP-resistant NSCLC tumor tissues and cell lines (A549/DDP and H1299/DDP). Knockdown of HOTAIR decreased the acquired cisplatin resistance of A549/DDP and H1299/DDP cells, as evidenced by attenuated 50% inhibitory concentration (IC50) of DDP, cell proliferation, migration and invasion in vitro, as well as tumor growth inhibition in vivo. Mechanically, HOTAIR negatively regulated miR-149-5p expression via targeting, and DCLK1 was a downstream target for miR-149-5p. DCLK1 was indirectly regulated by HOTAIR in DDP-resistant NSCLC cells as well. Functionally, miR-149-5p deletion could counteract the inhibitory effect of HOTAIR knockdown on cisplatin resistance; contrarily, restoring miR-149-5p exhibited the similar inhibition on cisplatin resistance in DDP-resistant cells in vitro, which was then abated by DCLK1 upregulation. CONCLUSION: Knockdown of HOTAIR enhances DDP-resistant NSCLC cells to overcome cisplatin resistance partially via regulating miR-149-5p/DCLK1 axis.

Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines.

Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer.