Tmem39b promotes tumor progression and sorafenib resistance by inhibiting ferroptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) poses a significant threat to human health. Resistance to sorafenib in the chemotherapy of HCC is a common and significant issue that profoundly impacts clinical treatment. While several members of the transmembrane (TMEM) protein family have been implicated in the occurrence and progression of HCC, the association between TMEM39b and HCC remains unexplored. This study revealed a significant overexpression of TMEM39b in HCC, which correlated with a poor prognosis. Subsequent investigation revealed that RAS-selective lethal 3 (RSL3) induced pronounced ferroptosis in HCC, and knocking down the expression of TMEM39b significantly decreased its severity. Similarly, following the induction of ferroptosis in HCC by sorafenib, knocking down the expression of TMEM39b also decreased the severity of ferroptosis, enhancing HCC tolerance to sorafenib. In conclusion, we propose that TMEM39b promotes tumor progression and resistance to sorafenib by inhibiting ferroptosis in HCC.

Effects of calcitonin on lumbar spinal stenosis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: There is some controversy about the effects of calcitonin (CT) on lumbar spinal stenosis (LSS). This systematic review and meta-analysis is to assess the strength of the evidence supporting the use of CT in the treatment of patients with LSS. MATERIAL AND METHOD: We performed an electronic search depicting randomized controlled trials (RCTs) through 4 databases from the date of database creation to January 2023. 3 different researchers conducted independent literature screening, data extractions, and quality assessments. The outcome measures included visual analogue scale (VAS), walking distance, and oswestry disability index (ODI). Meta-analysis and trial sequence analysis (TSA) were carried out using RevMan 5.4, Stata 16.0, and TSA 0.9. GRADE 3.6 was used to evaluate the evidence quality. RESULTS: We accepted 9 studies with 496 participants. The meta-analysis revealed that CT offered no significant improvement in VAS, walking distance, or ODI in patients with LSS. CONCLUSION: There is no evidence that CT has a benefit in patients with LSS, either alone or in combination with other treatments, or depending on the route of administration, according to the systematic review and meta-analysis of relevant RCTs.

An antihypertensive drug-AT1 inhibitor attenuated BRCA development promoted by chronic psychological stress via Ang II/PARP1/FN1 pathway.

Chronic psychological stress contributes to the occurrence of cancer and activates the renin-angiotensin system (RAS). However, the mechanisms by which RAS promotes the progression of breast cancer (BRCA) under chronic psychological stress are remain unknown. In this study, we observed elevated levels of Angiotensin II (Ang II) in both serum and BRCA tissue under chronic stress, leading to accelerated BRCA growth in a mouse model. An antihypertensive drug, candesartan (an AT1 inhibitor), effectively attenuated Ang II-induced cell proliferation and metastasis. Utilizing mass spectrometry and weighted gene co-expression network analysis (WGCNA), we identified fibronectin 1 (FN1) as the hub protein involved in chronic stress-Ang II/AT1 axis. Focal adhesion pathway was identified as a downstream signaling pathway activated during the progression of chronic stress. Depletion of FN1 significantly attenuated Ang II-induced proliferation and metastasis of BRCA cells. Poly (ADP-ribose) polymerase 1 (PARP1) was found to bind to the DNA promoter of FN1, leading to the transcription of FN1. Ang II upregulated PARP1 expression, resulting in increased FN1 levels. Recombinant FN1 partially restored the progress of BRCA malignancy induced by the Ang II/PARP1 pathway. In vivo, candesartan reversed the progressive effect of chronic psychological stress on BRCA. In clinical samples, Ang II levels in both serum and tumor tissues are higher in stressed patients compared to control patients. Serum Ang II levels were positively correlated with chronic stress indicators. In conclusion, our study demonstrated that chronic psychological stress accelerates the malignancy of BRCA, and the AT1 inhibitor candesartan counteracts these effects by suppressing the Ang II-AT1 axis and the downstream PARP1/FN1/focal adhesion pathway.

ASIC1a contributes to the epithelial-mesenchymal transformation of breast cancer by activating the Ca2+ /ß-catenin pathway.

Breast cancer is the most common cancer in the world, with metastasis being one of the leading causes of death among patients. The acidic environment of breast cancer tissue promotes tumor cell invasion and migration by inducing epithelial-mesenchymal transformation (EMT) in tumor cells, but the exact mechanisms are not yet fully understood. This study investigated the expression of acid-sensitive ion channel 1a (ASIC1a) in breast cancer tissue samples and explored the mechanisms by which ASIC1a mediates the promotion of EMT in breast cancer cells in an acidic microenvironment through in vivo and in vitro experiments. The results showed that first, the expression of ASIC1a was significantly upregulated in breast cancer tissue and was correlated with the TNM (tumor node metastasis) staging of breast cancer. Furthermore, ASIC1a expression was higher in tumors with lymph node metastasis than in those without. Second, the acidic microenvironment promoted [Ca2+ ]i influx via ASIC1a activation and regulated the expression of ß-catenin, Vimentin, and E-cadherin, thus promoting EMT in breast cancer cells. Inhibition of ASIC1a activation with PcTx-1 could suppress EMT in breast cancer cells. Finally, in vivo studies also showed that inhibition of ASIC1a could reduce breast cancer metastasis, invasion, and EMT. This study suggests that ASIC1a expression is associated with breast cancer staging and metastasis. Therefore, ASIC1a may become a new breast cancer biomarker, and the elucidation of the mechanism by which ASIC1a promotes EMT in breast cancer under acidic microenvironments provides evidence for the use of ASIC1a as a molecular target for breast cancer treatment.

Multivariate response surface methodology assisted modified QuEChERS method for the rapid determination of 39 pesticides and metabolites in medlar.

A modified QuEChERS method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for residue analysis of 39 pollutants (34 commonly used multi-class pesticides and 5 metabolites) in medlar matrices (fresh, dried, and medlar juice). Samples were extracted using water with 0.1 % formic acid: acetonitrile (5: 10, v/v). The phase-out salts and five different cleanup sorbents (including N-propyl ethylenediamine (PSA), octadecyl silane bonded silica gel (C18), graphitized carbon black (GCB), Carbon nanofiber (C-Fiber) and MWCNTs) were investigated to improve the purification efficiency. The Box-Behnken Design (BBD) study was employed for an optimal solution of the volume of extraction solvent, phase-out salt, and the purification sorbents for the analytical method. The average recoveries of the target analytes in the three medlar matrices ranged from 70 % to 119 % with relative standard deviations (RSDs) of 1.0 %-19.9 %. Screening of market samples (fresh and dried medlars) collected from the major producing regions in China showed that 15 pesticides and metabolites were detected in the samples at concentrations of 0.01-2.22 mg/kg, and none of which exceeded the maximum residue limits (MRLs) set in China. The results showed that the risk of food safety by consumption of medlar products caused by the use of pesticides was low. The validated method could be used for rapid and accurate screening of multi-class multi-pesticide residues in Medlar for food safety.

Carboxypeptidase Vitellogenic-Like Promotes the Proliferation and Metastasis of Osteosarcoma through the TGF-ß/Smad Signaling Pathway.

OBJECTIVE: This research explored the biological role and underlying mechanisms of carboxypeptidase vitellogenic-like (CPVL) in the progression of osteosarcoma. METHODS: Through mining of microarray data from the GEO database and utilization of qRT-PCR and Western blot analyses, CPVL expression in osteosarcoma tissues and cells was evaluated. RNA interference and lentiviral transduction techniques were applied to edit the CPVL gene. RNA-seq was used to screen for the downstream target genes of CPVL. RESULTS: In both osteosarcoma biopsy samples and cell lines, the expression of CPVL was abnormally higher than that in normal cells or osteoblasts. CPVL silencing notably inhibited the proliferative activity of osteosarcoma cells, whereas CPVL overexpression had the opposite effect. CPVL silencing had potent tumor-suppressive ability in a xenograft osteosarcoma model in nude mice. CPVL silencing significantly suppressed osteosarcoma cell migration, invasion and EMT, whereas CPVL overexpression accelerated these events. Downstream genes related to the occurrence and development of osteosarcoma, including TGF-ß/Smad signaling pathway molecules (TGF-ß2, TGF-ßR1, Smad2/3, and Smad5), were suppressed by CPVL silencing. CONCLUSIONS: High CPVL expression in osteosarcoma not only promoted tumor growth but also induced the EMT process through the TGF-ß/Smad signaling pathway. CPVL may be a new antitumor therapeutic target for osteosarcoma.

Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma.

Although some advances have been made in the treatment of osteosarcoma in recent years, surgical resection remains the mainstream treatment. Initial and early diagnosis of osteosarcoma could be very difficult to achieve due to the insufficient sensitivity for the means of examination. The distal metastasis of osteosarcoma also predicts the poor prognosis of osteosarcoma. In order to solve this series of problems, people begin to discover a new method of diagnosing and treating osteosarcoma. Ubiquitination, as an emerging posttranslational modification, has been shown to be closely related to osteosarcoma in studies over the past decades. In general, this review describes the cellular functions and molecular mechanisms of ubiquitination during the development of osteosarcoma.

Emerging Perspectives of Bone Metastasis in Hepatocellular Carcinoma.

Recent evidence suggests the global incidence and mortality of hepatocellular carcinoma (HCC) are increasing. Although the highest incidence of HCC remains entrenched in WHO regions with high levels of HBV-HCV infection, the etiology of this disease is rapidly changing to include other lifestyle risk factors. Extrahepatic metastasis is a frequent feature of advanced HCC and most commonly locates in the lungs and bone. Bone metastasis in HCC (HCC-BM) signals a more aggressive stage of disease and a poorer prognosis, simultaneously HCC-BM compromises the function and integrity of bone tissue. HCC induced osteolysis is a prominent feature of metastasis that complicates treatment needed for pathologic fractures, bone pain and other skeletal events like hypercalcemia and nerve compression. Early detection of bone metastases facilitates the treatment strategy for avoiding and relieving complications. Although recent therapeutic advances in HCC like targeting agents and immunotherapy have improved survival, the prognosis for patients with HCC-BM remains problematic. The identification of critical HCC-BM pathways in the bone microenvironment could provide important insights to guide future detection and therapy. This review presents an overview of the clinical development of bone metastases in HCC, identifying key clinical features and identifying potential molecular targets that can be deployed as diagnostic tools or therapeutic agents.

Peroral endoscopic longer vs shorter esophageal myotomy for achalasia treatment: A systematic review and meta-analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) has been demonstrated to be safe and effective in the treatment of achalasia. Longer myotomy is the standard POEM procedure for achalasia but when compared with shorter myotomy, its effectiveness is not as well known. AIM: To compare the clinical effectiveness of longer and shorter myotomy. METHODS: PubMed, EmBase, Cochrane Library, web of science and clinicaltrials.gov were queried for studies comparing shorter and longer POEM for achalasia treatment. The primary outcome was clinical success rate. Secondary outcomes comprised of operative time, adverse events (AEs) rate, gastroesophageal reflux disease (GERD) and procedure-related parameters. The Mantel-Haenszel fixed-effects model was primarily used for the analysis. Publication bias was assessed. RESULTS: Six studies were included in this analysis with a total of 514 participants. During the follow-up period of 1-28.7 mo, longer and shorter myotomy in treating achalasia showed similar excellent effectiveness [overall clinical success (OR = 1, 95%CI: 0.46-2.17, P = 1, I2: 0%; subgroup of abstract (OR = 1.19, 95%CI: 0.38 to 3.73; P = 0.76; I2: 0%); subgroup of full text (OR = 0.86 95%CI: 0.30 to 2.49; P = 0.78; I2: 0%)]. Shorter myotomy had significantly reduced mean operative time compared with the longer procedure. There were no statistically significant differences in AEs rates, including GERD (overall OR = 1.21, 95%CI: 0.76-1.91; P = 0.42; I2: 9%; subgroup of abstract OR = 0.77, 95%CI: 0.40-1.47; P = 0.43; I2: 0%; subgroup of full text OR = 1.91, 95%CI: 0.98-3.75; P = 0.06; I2: 0%), hospital stay (overall MD = -0.07, 95%CI: -0.30 to 0.16; P = 0.55; I2: 24%; subgroup of abstract MD = 0.20, 95%CI: -0.25 to 0.65; P = 0.39; I2: 0; subgroup of full text MD = -0.16, 95%CI: -0.42 to 0.10; P = 0.23; I2: 42%), and major bleeding (overall OR = 1.25, 95%CI: 0.58-2.71; P = 0.56; I2: 0%) between the two procedures. These differences remained statistically non-significant in all sensitivity analyses. CONCLUSION: POEM was effective in treating achalasia. Shorter and longer myotomy procedures provided similar therapeutic effects in terms of long-term effectiveness. In addition, shorter myotomy reduced the operative time.

Metabolomics analysis of cucumber fruit in response to foliar fertilizer and pesticides using UHPLC-Q-Orbitrap-HRMS.

Pesticides and fertilizers are often used to improve the yield and quality of cucumber fruit. In this study, the effect of pesticide applied with or without foliar fertilizer on the cucumber fruit metabolism was investigated. The results showed that the mixed use of pesticides and foliar fertilizer could significantly increase the contents of organic acids and the antioxidant level. When pesticide was used without foliar fertilizer, cucumber fruit up-regulated (1.3 times) shikimate-phenylpropanoid pathway and improved the antioxidant capacity to deal with the pesticide stress. However, the tricarboxylic acid cycle was up-regulated 1.1 times and the antioxidant capacity was improved to promote the pesticide dissipation when pesticide was applied with foliar fertilizer. These observations indicate that the mixed application of foliar fertilizer and pesticides can regulate related metabolites and metabolic pathways, improve the quality and antioxidant capacity of cucumber fruit, and promote the dissipation of pesticides.

Development, optimization, and validation of a method for detection of cartap, thiocyclam, thiosultap-monosodium, and thiosultap-disodium residues in plant foods by GC-ECD.

A method was developed for the simultaneous determination of four nereistoxin-related pesticides, viz. cartap, thiocyclam, thiosultap-monosodium, and thiosultap-disodium, in 20 plant foods. The samples were extracted using a hydrochloric acid solution containing cysteine hydrochloride, derivatized to nereistoxin under alkaline conditions, and analyzed by gas chromatography with electron capture detector. The average recoveries of the method were 72-108%, with relative standard deviations (RSDs) of 0.3-14.7% (n = 1200, p < 0.05). The intermediate precision and reproducibility experiments using established methods were also carried out. All the results passed the Cochrane and Grubbs tests (n = 2400, p < 0.05). The RSDs of intermediate precision and RSDs of reproducibility among laboratories were in the ranges 1.7-10.9% and 2.4-15.3% (n = 2400, p < 0.05), respectively, indicating that the accuracy and precision of the method are satisfactory. This method can be used to detect nereistoxin-related pesticides in plant foods.

Nanocomposite coating of albumin/Li-containing bioactive glass nanospheres promotes osteogenic activity of PEEK.

Polyetheretherketone (PEEK) is an important material applied in orthopedic applications, as it posses favorable properties for orthopedic implants, e.g., radiolucency and suitable elastic modulus. However, PEEK exhibits insufficient osteogenesis and osteointegration that limits its clinical applications. In this study, we aimed to enhance the osteogenisis of PEEK by using a surface coating approach. Nanocomposite coating composed of albumin/lithium containing bioactive glass nanospheres was fabricated on PEEK through dip-coating method. The presence of nanocomposite coating on PEEK was confirmed by SEM, FTIR, and XRD techniques. Nanocomposite coatings significantly enhanced hydrophilicity and roughness of PEEK. The nanocomposite coatings also enhanced adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells due to the presence of bioactive glass nanospheres and the BSA substrate film. The results indicate the great potential of the nanocomposite coating in enhancing osteogenesis and osteointegration of PEEK implants.

Radiosensitizing effect of gold nanoparticle loaded with small interfering RNA-SP1 on lung cancer: AuNPs-si-SP1 regulates GZMB for radiosensitivity.

Radioresistance is a major challenge that largely limits the efficacy of radiotherapy in lung cancer. Gold nanoparticles (AuNPs) are emerging as novel radiosensitizers for cancer patients. Therefore, this study was designed to explore the radiosensitizing effect and mechanism of AuNPs loaded with small interfering RNA (siRNA)-SP1 (AuNPs-si-SP1) on lung cancer. AuNPs-si-SP1 was prepared by the noncovalent binding between AuNPs and siRNA-SP1. The adsorption capacity of AuNPs to siRNA-SP1 was analyzed by gel electrophoresis. The cell uptake of AuNPs-si-SP1 was observed under a laser confocal microscopy. Silencing efficacy of AuNPs-si-SP1 was validated by RT-qPCR and Western blot analysis. Cell viability was determined by CCK-8 assay, radiosensitization by plate colony formation assay, cell apoptosis and cell cycle by flow cytometry, and DNA double strand breaks by immunofluorescence in the presence or absence of AuNPs-si-SP1 or GZMB. The downstream mechanism of SP1 was predicted by bioinformatics analysis, followed by verification by Western blot analysis. Subcutaneous tumorigenesis in nude mice was established to verify the radiosensitization of AuNPs-si-SP1 and GZMB in vivo. AuNPs-si-SP1 effectively absorbed SP1 siRNA and was highly internalized by A549 cells to reduce SP1 protein expression. AuNPs-si-SP1 or GZMB overexpression promoted cells to G2/M phase, DNA double strand breaks, and enhanced radiosensitivity. SP1 could repress GZMB expression in lung cancer cells. In vivo experiments manifested that AuNPs-si-SP1 could inhibit the growth of solid tumor in nude mice to achieve radiosensitization by inhibiting SP1 to upregulate GZMB. AuNPs-si-SP1 might increase the radiosensitivity of lung cancer by inhibiting SP1 to upregulate GZMB.

Downregulation of long non-coding RNA MR4435-2HG suppresses breast cancer progression via the Wnt/ß-catenin signaling pathway.

Extensive research has contributed to the current understanding of the critical roles played by long non-coding RNAs in various types of cancer. The present study aimed to investigate the function and mechanism of the long non-coding RNA, MIR4435-2HG (also termed LINC00978), in breast cancer growth and metastasis. Using Gene Expression Profiling Interactive Analysis, an online web tool, it was revealed that MIR4435-2HG was upregulated in breast cancer tissue, and its high expression was associated with poor prognosis based on The Cancer Genome Atlas database. MIR4435-2HG knockdown increased cell apoptosis but decreased cell proliferation, migration and invasion. MIR4435-2HG knockdown increased pro-apoptotic protein expression but decreased anti-apoptotic protein expression. In addition, MIR4435-2HG knockdown leads to dysregulation of epithelial-to-mesenchymal transition-associated genes. Furthermore, knockdown of MIR4435-2HG results in inactivation of the Wnt/ß-catenin signaling pathway. The results of the present study demonstrate the tumor-promoting role of MIR4435-2HG in breast cancer progression.

Dynamics and risk assessment of pesticides in cucumber through field experiments and model simulation.

Pesticides are often applied multiple times during cucumber cultivation in China. In order to obtain the residue concentrations and subsequently human health risk assessment after pesticide multiple applications, plenty of field trials have been conducted, consuming a lot of labor force and funds. The application of kinetic models can address this problem to some extent by predicting the residue values of pesticides in cucumber. In this study, a dynamic model (dynamiCROP) was applied in combination with field experiments to investigate the distribution, translocation, and dissipation after the one-time application of seven pesticides in a cucumber-soil environment. Moreover, the residue concentrations after the second and third applications of the seven pesticides were estimated through a "simple superposition method", i.e., superimposing the output results of dynamiCROP after each single pesticide application. The estimated residue concentrations show good agreement with that measured through field experiments with R2 = 0.865 and relative root mean squared error (RRMSE) = 13.2%. Meanwhile, the short- and long-term risks of each pesticide were assessed according to the concentrations estimated by the "simple superposition method" with the dynamiCROP model. It shows that the seven pesticides, applied multiple times during cucumber cultivation, pose a very low dietary risk to human health through cucumber intake. Our study presents a cost- and time-efficient way to investigate the dissipation of pesticides in the cucumber-soil environment, predicate the residue concentrations of pesticides after multiple applications and assess the dietary risk of pesticides to human health through cucumber intake.

A Comprehensive Evaluation of ZrC Nanoparticle in Combined Photothermal and Radiation Therapy for Treatment of Triple-Negative Breast Cancer.

Because of the difficulty in treating triple-negative breast cancer (TNBC), the search for treatments has never stopped. Treatment opinions remain limited for triple-negative breast cancer (TNBC). The current treatment approach of using photothermal therapy (PTT) is often imprecise and has limited penetration below the surface of the skin. On the other hand, radiation therapy (RT) has its unavoidable disadvantages, such as side effects or ineffectiveness against hypoxic tumor microenvironment (TME). In this study, we proposed the use of ZrC nanoparticles in conjunction with RT/PTT to enhance antitumor and antimetastatic effect. We modified the ZrC nanoparticle with bovine serum albumin (BSA) and folic acid (FA), sizing desirable about 100nm. The photothermal conversion efficiency was calculated to be 40.51% and sensitizer enhancement ration (SER) was 1.8. With addition of ZrC NPs, more DNA were damaged in γ-H2AX and more ROS were detected with immunofluorescence. In vitro and vivo, the combined therapy with ZrC NPS showed the best effect of tumor cell inhibition and safety. Our results provide evidence that the combination of ZrC NPs, PT, and RT is effective in of TNBC, making it a great potential application for cancer therapy in clinic.

Erythrocyte membrane protein band 4.1-like 3 inhibits osteosarcoma cell invasion through regulation of Snai1-induced epithelial-to-mesenchymal transition.

Erythrocyte membrane protein band 4.1-like 3 (EPB41L3) is an important membrane skeletal protein that may interact with numerous membrane proteins. Loss of EPB41L3 is reported in multiple cancer types, and it is originally identified as a tumor suppressor. In this study, through analyzing expression profiling retrieved from the Gene Expression Omnibus (GEO) dataset, we find that EPB41L3 is upregulated in primary osteosarcoma (OS) and osteosarcoma cell lines. Importantly, EPB41L3 may promote osteosarcoma cell proliferation and suppress osteosarcoma cell migration and invasion. Reduced EPB41L3 leads to a decrease of E-cadherin as well as an increase of N-cadherin and Vimentin, implying a prominent epithelial-to-mesenchymal transition. Furthermore, we demonstrate that EPB41L3 inhibits the epithelial-to-mesenchymal transition through destabilizing the Snai1 protein, one of the most important transcription factors of the epithelial-to-mesenchymal transition process. Collectively, our study has first established the complex and vital roles of EPB41L3 and implicated EPB41L3 as a potential biomarker in osteosarcoma.

circKMT2D contributes to H2O2-attenuated osteosarcoma progression via the miR-210/autophagy pathway.

Circular RNAs (circRNAs) have been demonstrated to be involved in osteosarcoma (OS) development; however, the underlying mechanism of circKMT2D in OS progression remains unclear. The present study aimed to elucidate how circKMT2D could affect hydrogen peroxide (H2O2)-induced OS progression. H2O2 (100 µmol/l) was used to treat MG63 and U2OS cells. The cell viability, invasive ability, apoptosis and circKMT2D expression were detected using Cell Counting Kit-8 assay, Transwell assay, flow cytometry and reverse transcription-quantitative PCR, respectively. Furthermore, MG63 and U2OS cells transfected with circKMT2D short hairpin RNA and negative control were treated with H2O2, and circKMT2D expression and cell phenotype were determined. Dual-luciferase reporter assay was conducted to determine the association between circKMT2D and miR-210 expression level. Rescue experiments were conducted to examine the mechanisms through which circKMT2D and miR-210 could affect H2O2-treated MG63 cells. In addition, the effects of miR-210 on the expression of the autophagy-related proteins Beclin1 and p62 in H2O2-treated MG63 cells were detected by western blotting. An autophagy inhibitor was used to treat the MG63 cells, and whether miR-210 could affect the H2O2-treated MG63 cell phenotype through autophagy was investigated. The results demonstrated that H2O2 treatment promoted cell apoptosis and decreased cell viability, invasive ability and circKMT2D expression in MG63 and U2OS cells. Furthermore, circKMT2D knockdown decreased the cell viability and invasive ability and enhanced the apoptosis of H2O2-treated MG63 and U2OS cells. circKMT2D possessed binding sites for miR-210 and inhibited miR-210 expression. In H2O2-treated MG63 cells, miR-210 silencing partially reversed the circKMT2D knockdown-induced cell viability inhibition and apoptosis promotion. In addition, miR-210 elevated Beclin1 expression and decreased p62 expression in H2O2-treated MG63 cells. The use of the autophagy inhibitor partially reversed the miR-210 overexpression-induced promotion of apoptosis and inhibition of the viability and invasive ability of H2O2-treated MG63 cells. Taken together, these findings indicated that circKMT2D knockdown may contribute to the inhibition of H2O2-attenuated OS progression via miR-210/autophagy pathway.

Loss of histone H4 lysine 20 trimethylation in osteosarcoma is associated with aberrant expression ofhistone methyltransferase SUV420H2.

Epigenetic modifications of histones have crucial roles in various types of cancers. The aberrant trimethylation of histone H4 at lysine 20 (H4K20) has been implicated in carcinogenesis. At present, the status of trimethylation at H4k20 (H4K20me3) in osteosarcoma (OS), the predominant bone cancer in humans, is unknown. In the present study, a genome-wide decrease was observed in H4K20me3 levels in OS tissues and cell lines. Reduced levels of lysine methyltransferase 5C (SUV420H2), the histone methyltranferase responsible for modification of H4K20me3, was also observed in OS cells with the associated loss of H4K20me3. Furthermore, a total of 507 SUV420H2-regulated genes were identified through RNA-seq and a number of candidate genes were further validated. Bioinformatic analysis revealed an association between SUV420H2 and multiple signaling pathway, including the mitogen-activated protein kinase, P53, transforming growth factor and the ErbB pathways. These results demonstrated that there are aberrant levels of H4K20me3 and SUV420H2 in OS, and highlighted H4K20me3 as a candidate biomarker for the early detection of OS.