Analyzing the pressure resistant, sublethal injury and resuscitable viable but non-culturable state population of Escherichia coli, Staphylococcus aureus, Bacillus amyloliquefaciens and Lactiplantibacillus plantarum under high pressure processing.

This study aimed to analyze and reduce the pressure resistance (PR), sublethal injury (SLI), and viable but non-culturable (VBNC) populations during HPP. Escherichia coli, Staphylococcus aureus, Bacillus amyloliquefaciens and Lactiplantibacillus plantarum were selected for evaluation of PR, SLI and VBNC cell counts and proportions during HPP. The results revealed that the bactericidal efficiency against these strains gradually improved as the processing pressure increased. However, viable bacteria could still be detected, suggesting that there may involve the presence of resistant population that difficult to be killed or revived from SLI. Further detecting the quantity and proportion of PR, SLI and VBNC bacteria found that these state of cells were present during whole HPP treatment. Additionally, the more resistant a bacterial species was to high pressure, the fewer SLI and more resuscitable VBNC (RVBNC) populations it generated, and vice versa. Therefore, correlation analysis was also employed to make the relationship between log reduction, SLI and RVBNC population ratios clearer. The results demonstrated that the log reduction was highly positive correlation with SLI population ratios, and negative correlation with RVBNC population within our detected species at 500 MPa. Furthermore, CO2 and Nisin were employed to combined with HPP to reduce these survivors. Comparing with 233, 218, 241 and 259 MPa for HPP treatment, it took 37, 89, 135 and 229 MPa for HPP + CO2, and 189, 161, 199 and 292 MPa for HPP + Nisin to the first decimal reduction for E. coli, S.aureus, B. amyloliquefaciens and L. plantarum, respectively. The results indicated that HPP combined with CO2 or Nisin could significantly reduce the quantity of PR, SLI, and RVBNC cells during HPP, and provide better bactericidal effects. In conclusion, we quantified the presence of PR, SLI, and VBNC bacteria after high pressure treatment and investigate the effectiveness of HPP combined with CO2 or Nisin to enhance the inactivation of bacteria and reduce the occurrence of PR, SLI, and RVBNC bacteria.

Anticancer or carcinogenic? The role of estrogen receptor ß in breast cancer progression.

Estrogen receptor ß (ERß) is closely related to breast cancer (BC) progression. Traditional concepts regard ERß as a tumor suppressor. As studies show the carcinogenic effect of ERß, some people have come to a new conclusion that ERß serves as a tumor suppressor in estrogen receptor α (ERα)-positive breast cancer, while it is a carcinogen in ERα-negative breast cancer. However, we re-examine the role of ERß and find this conclusion to be misleading based on the last decade's research. A large number of studies have shown that ERß plays an anticancer role in both ERα-positive and ERα-negative breast cancers, and its carcinogenicity does not depend solely on the presence of ERα. Herein, we review the anticancer and oncogenic effects of ERß on breast cancer progression in the past ten years, discuss the mechanism respectively, analyze the main reasons for the inconsistency and update ERß selective ligand library. We believe a detailed and continuously updated review will help correct the one-sided understanding of ERß, promoting ERß-targeted breast cancer therapy.

Retraction Notice to: Inflammatory-Related P62 Triggers Malignant Transformation of Mesenchymal Stem Cells through the Cascade of CUDR-CTCF-IGFII-RAS Signaling.

[This retracts the article DOI: 10.1016/j.omtn.2018.03.002.].

Estrogen receptor ß-targeted hypoxia-responsive near-infrared fluorescence probes for prostate cancer study.

Aberrant expression of estrogen receptor ß (ERß) and tumor hypoxia have been observed in castration-resistant prostate cancer (CRPC); therefore, hypoxia-responsive labeling of ERß will be beneficial for the early diagnosis and treatment of CRPC. Herein, we report the first ERß-targeted hypoxia-responsive near-infrared fluorescent probes, which showed superior ERß selectivity and favorable optical properties. These two probes exhibited excellent hypoxia responsiveness and specific mitochondrial ERß imaging ability in CRPC cells. In addition, P1 displayed strong anti-interference ability and good tumor imaging capacity in vivo, contributing to effective diagnosis of CRPC. Mechanistic studies, including high resolution mass spectrometry (HRMS) and density functional theory (DFT) calculations, showed that the introduction of a nitro group quenched the probe fluorescence by inducing a PET effect, while in the hypoxic tumor microenvironment, reduction of the nitro group blocked the PET effect and turned on the probe fluorescence. These novel ERß-targeted hypoxia-responsive near-infrared fluorescent probes may promote the study of prostate cancer.

Effect of maternal body mass index on the prophylactic dose of phenylephrine for preventing hypotension in parturients after spinal anaesthesia.

BACKGROUND: To compare the median effective dose (ED50) of phenylephrine for prophylactic continuous infusion in parturients with different body mass indices (BMIs) during combined spinal-epidural anaesthesia for caesarean section and to investigate the impact of maternal BMI on the prophylactic dose of phenylephrine. METHODS: Parturients receiving combined spinal-epidural anaesthesia for elective caesarean section were divided into a standard group (Group S, BMI < 30 kg/m2) and an obesity group (Group O, BMI > 30 kg/m2), each with 30 patients. A sequential allocation design was used to administer the prophylactic infusion of phenylephrine after the completion of a spinal anaesthetic injection to prevent hypotension (defined as a reduction of systolic blood pressure ≥ 20% of the baseline value or systolic blood pressure < 90 mmHg), with an initial infusion rate of 50 µg/min for the first parturient subsequent adjusted up or down by 10 µg/min depending on whether the previous parturient developed hypotension or not during the study period. The Dixon and Massey method and the isotonic regression method were used to calculate and compare the ED50 and 95% confidence interval (CI) of phenylephrine between the two groups. RESULTS: The results were 21.92 µg/min (95% CI, 14.90-28.94 µg/min) for Group S and 42.14 µg/min (95% CI, 24.58-59.70 µg/min) for Group O. The ratio of relative potency of Group O to Group S is 1.92 (95% CI 1.09-3.14), P = 0.034. CONCLUSIONS: The dose of phenylephrine for the prevention of hypotension after spinal anaesthesia for caesarean section is dependent on maternal BMI. Therefore, a weight-based phenylephrine dose is reasonable.

Study on the associated factors of turnover intention among emergency nurses in China and the relationship between major factors.

BACKGROUND: In China, the demand for emergency medical services is increasing. However, there is a shortage of nurses and a high turnover rate. The study has three purposes: (1) to investigate the turnover intention of emergency nurses in China; (2) to analyze the associated factors of turnover intention; and (3) to clarify the relationship between work stress, job burnout, perceived organization support, job satisfaction and turnover intention. METHODS: A cross-sectional study was conducted to investigate 56 hospitals with independent emergency departments in Chongqing. A total of 522 emergency nurses were included. Descriptive statistics, One-way analysis of variance, Pearson correlated analysis and a mediation regression analysis were used to analyze the turnover intention, associated factors, and the relationship between the major study variables. RESULTS: The score of turnover intention was 2.38 ± 0.57, and the proportion of nurses with high turnover intention was 40.61%. Age, working years in emergency department (ED), marital status, employment forms, professional title, promotion opportunities, weekly working hours, monthly night shifts and exposure to workplace violence during the year influenced turnover intention of emergency nurses. Work stress and job burnout were positively correlated with turnover intention (r = 0.189, r = 0.391), while perceived organization support and job satisfaction were negatively correlated with turnover intention (r = - 0.349, r = - 0.485). perceived organization support plays a mediating role between work stress and job burnout, between work stress and job satisfaction, and between work stress and turnover intention. CONCLUSION: Work stress, job burnout, perceived organization support and job satisfaction are important associated factors of emergency nurses' turnover intention in China. It is suggested to take intervention measures to reduce work stress and job burnout and to improve perceived organization support and job satisfaction.

Estrogen Receptor ß-Targeted Near-Infrared Inherently Fluorescent Probe: A Potent Tool for Estrogen Receptor ß Research.

Estrogen receptor ß (ERß) is associated with many diseases, and ERß probes can help to reveal the complex role of ERß and promote the development of ERß-targeted therapy. Herein, we designed and synthesized the first ERß-targeted near-infrared (NIR) inherently fluorescent probe P5, which showed the advantages of high ERß selectivity, good optical properties, and excellent ERß imaging capability in living cells. The probe was successfully utilized to explore ERß motion characteristic, and for the first time, the diffusion coefficient of ERß was obtained. Moreover, P5 was also successfully applied to the in vivo imaging of ERß in the prostate cancer mice model. Therefore, this ERß-targeted NIR probe might be employed as a potential tool for the research of ERß and related diseases.

New oral anticoagulants for nonvalvular atrial fibrillation with peripheral artery disease: a meta-analysis.

BACKGROUND: New oral anticoagulants (NOACs) are as effective and safe as warfarin for patients with non-valvular atrial fibrillation (NVAF). Limited evidence is available regarding outcomes for NVAF patients with peripheral artery disease (PAD). METHODS: A systematic search of Medline, Embase, and the Cochrane Library was performed. Two reviewers independently performed data extraction and quality assessment using the Cochrane Collaboration tool for assessing risk of bias. All primary publications and secondary analyses comparing NOACs with other oral anticoagulation regimens for the prevention of stroke in patients with both NVAF and PAD from phase III clinical trials were evaluated. The primary outcomes were stroke, systemic embolism (SE), major bleeding, and intracranial hemorrhage (ICH), and the secondary outcomes were cardiovascular (CV) mortality, all-cause mortality, and myocardial infarction (MI). RESULTS: Three articles were included in this study. The pooled results showed a relative risk for stroke/SE with NOACs of 0.86 (95% confidence interval [CI]: 0.53-1.39), for major bleeding, 1.12 (95% CI: 0.70-1.81), for ICH, 0.47 (95% CI: 0.16-1.36), for CV mortality, 0.77 (95% CI: 0.57-1.04), for all-cause mortality, 0.91 (95% CI: 0.70-1.19), and for MI, 1.10 (95% CI: 0.64-1.90). CONCLUSION: The findings show that NOACs are effective and safe for preventing stroke/SE in patients with both NVAF and PAD.

miR-433 Inhibits Neuronal Growth and Promotes Autophagy in Mouse Hippocampal HT-22 Cell Line.

Background: MicroRNAs (miRNAs) have an increasing functional role in some neurodegenerative diseases. Autophagy, the degradation of bulk protein in the cytoplasm, is the quality control function of protein and has a protective role in the survival of neural cells. miR-433 may play a regulatory role in neurodegenerative diseases. Many aspects underlying the mechanism of miR-433 in neural development and neurodegeneration are not clear. Methods: In this study, we established stable cell lines expressing miR-433 by infecting mouse hippocampal neural cell line (HT-22) cells with rLV-miR-433 and the control rLV-miR. Pre-miR-433 expression was analyzed using polymerase chain reaction (PCR). Mature miR-433 expression was measured using quantitative PCR (qPCR). The effect of miR-433 overexpression on cell proliferation was determined using a CCK-8 assay and flow cytometry. RNA interference was used to analyze the function of Cdk12 in mediating the effect of miR-433 on cell proliferation. The effect of miR-433 overexpression on cell apoptosis was determined by flow cytometry. Autophagy-related genes Atg4a, LC3B, and Beclin-1 were determined using qPCR, Western blot, or immunofluorescence. In addition, RNA interference was used to analyze the effect of Atg4a on the induction of autophagy. TargetScan 7.2 was used to predict the target genes of miR-433, and Smad9 was determined using qPCR. Results: Our results indicated that miR-433 increased the expression of Atg4a and induced autophagy by increasing the expression of LC3B-Ⅱ and Beclin-1 in an Atg4a-dependent manner. In addition, miR-433 upregulated the expression of Cdk12 and inhibited cell proliferation in a Cdk12-dependent manner and promoted apoptosis in HT-22 cells under the treatment of 10-hydroxycamptothecin. Conclusion: The results of our study suggest that miR-433 may regulate neuronal growth by promoting autophagy and attenuating cell proliferation. This might be a potential therapeutic intervention in neurodegenerative diseases.

New oral anticoagulants for nonvalvular atrial fibrillation with stable coronary artery disease: A meta-analysis.

BACKGROUND: New oral anticoagulants (NOACs) are effective and safe in patients with nonvalvular atrial fibrillation (NVAF). Limited evidence is available regarding outcomes for NVAF patients with stable coronary artery disease (CAD). METHODS: A systematic search of Medline, Embase, and the Cochrane Register was performed. Two reviewers independently performed data extraction and quality assessment using the Cochrane Collaboration risk-of-bias assessment tool. We evaluated all primary publications and secondary analyses comparing NOACs with any other OAC agent for preventing stroke in patients with both NVAF and stable CAD from phase III clinical randomized control trials. The primary outcomes were stroke, systemic embolism (SE), major bleeding, and intracranial hemorrhage (ICH), and the secondary outcomes were cardiovascular (CV) death, all-cause death, and myocardial infarction (MI). RESULTS: Four articles with a total of 19 266 patients were included in this study. The pooled results showed a relative risk for stroke/SE with NOACs of 0.83 (95% confidence interval [CI]: 0.71-0.97), for major bleeding 0.85 (95% CI: 0.63-1.14), for ICH 0.36 (95% CI: 0.19-0.54), for MI 1.00 (95% CI: 0.82-1.20), for CV death 0.94 (95% CI: 0.83-1.06), and for all-cause death 0.95 (95% CI: 0.85-1.07). CONCLUSION: NOACs were effective in preventing stroke/SE and reducing the risk of ICH in patients with both NVAF and CAD.

Establishment of evaluation criteria for the development of high quality ERα-targeted fluorescent probes.

ERα-targeted fluorescent probes are important tools for ERα study. In order to develop high quality ERα-targeted probes, a sound and complete evaluation system is essential but has not been established yet. Herein, we set up a series of evaluation criteria for ERα-targeted fluorescent probes including ERα binding affinity, fluorescence quantum yield, cytotoxicity, ERα tracking capacity, ERα selectivity and ERα labeling ability. To verify the practicability of the evaluation criteria, we designed and synthesized two ERα-targeted fluorescent probes and fully characterized their properties based on the proposed evaluation criteria. It showed that the probes exhibited better performance. Moreover, we applied the probes in MCF-7 cells to study the ERα motion characteristics for the first time. We hope that our evaluation criteria could be helpful for the establishment of a complete evaluation system for ERα-targeted fluorescent probes.

Rational design of ERα targeting hypoxia turn-on fluorescent probes with antiproliferative activity for breast cancer.

The overexpression of estrogen receptor (ER) α is not only closely related to the development of ER+ breast cancer, but is also an important biomarker for clinical diagnosis and treatment. Herein, we report several ERα targeting hypoxia turn-on fluorescent probes with antitumor activity for breast cancer cells. Among them, probes 3 and 5 displayed good ERα targeting ability and favorable hypoxia turn-on response in MCF-7 cells. Moreover, the probes 3 and 5 exhibited good antiproliferative activity towards MCF-7 cells (IC50 = 8.5 µM, 10.3 µM) and a much lower cytotoxicity to normal cells compared with the positive control. It is expected that these novel fluorescent probes may provide useful tools for the theranostics of ER+ breast cancer.

miR24-2 accelerates progression of liver cancer cells by activating Pim1 through tri-methylation of Histone H3 on the ninth lysine.

Several microRNAs are associated with carcinogenesis and tumour progression. Herein, our observations suggest both miR24-2 and Pim1 are up-regulated in human liver cancers, and miR24-2 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR24-2 increases the expression of N6-adenosine-methyltransferase METTL3 and thereafter promotes the expression of miR6079 via RNA methylation modification. Furthermore, miR6079 targets JMJD2A and then increased the tri-methylation of histone H3 on the ninth lysine (H3K9me3). Therefore, miR24-2 inhibits JMJD2A by increasing miR6079 and then increases H3K9me3. Strikingly, miR24-2 increases the expression of Pim1 dependent on H3K9me3 and METTL3. Notably, our findings suggest that miR24-2 alters several related genes (pHistone H3, SUZ12, SUV39H1, Nanog, MEKK4, pTyr) and accelerates progression of liver cancer cells through Pim1 activation. In particular, Pim1 is required for the oncogenic action of miR24-2 in liver cancer. This study elucidates a novel mechanism for miR24-2 in liver cancer and suggests that miR24-2 may be used as novel therapeutic targets of liver cancer.

Long noncoding RNA HULC accelerates the growth of human liver cancer stem cells by upregulating CyclinD1 through miR675-PKM2 pathway via autophagy.

BACKGROUND: The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells. METHODS: Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed. RESULTS: We demonstrate that HULC promotes growth of liver cancer stem cells in vitro and in vivo. Mechanistically, HULC enhances the expression of Sirt1 dependent on miR675 and then induces the cellular autophagy through Sirt1. HULC enhances CyclinD1 and thereby increases pRB and inhibited P21 WAF1/CIP 1 via autophagy-miR675-PKM2 pathway in human liver cancer stem cells. Ultimately, our results demonstrate that CyclinD1 is required for the oncogenic functions of HULC in liver cancer stem cells. CONCLUSIONS: It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.

Chitosan Derivatives and Their Application in Biomedicine.

Chitosan is a product of the deacetylation of chitin, which is widely found in nature. Chitosan is insoluble in water and most organic solvents, which seriously limits both its application scope and applicable fields. However, chitosan contains active functional groups that are liable to chemical reactions; thus, chitosan derivatives can be obtained through the chemical modification of chitosan. The modification of chitosan has been an important aspect of chitosan research, showing a better solubility, pH-sensitive targeting, an increased number of delivery systems, etc. This review summarizes the modification of chitosan by acylation, carboxylation, alkylation, and quaternization in order to improve the water solubility, pH sensitivity, and the targeting of chitosan derivatives. The applications of chitosan derivatives in the antibacterial, sustained slowly release, targeting, and delivery system fields are also described. Chitosan derivatives will have a large impact and show potential in biomedicine for the development of drugs in future.

miR24-2 Promotes Malignant Progression of Human Liver Cancer Stem Cells by Enhancing Tyrosine Kinase Src Epigenetically.

MicroRNA24-2 (miR24-2) is associated with human tumorigenesis; however, its molecular mechanisms are poorly understood. Herein, our findings demonstrate that miR24-2 promotes the proliferation ability in vitro and the tumorigenic ability in vivo in human liver cancer stem cells (hLCSCs). Mechanically, the miR24-2 targets for 3' UTR (2,627-2,648) of protein arginine methyltransferase 7 (PRMT7) inhibit the translational ability of prmt7 gene. Moreover, miR24-2 inhibits the di-/tri-methylation of histone H4 arginine 3 by reducing PRMT7 and then promotes the expression of Nanog via long noncoding RNA HULC. Notably, miR24-2 inhibits histone deacetylase HDAC3 through miR675, which promotes the acetylation of histone H4 at lysine 16. Subsequently, miR24-2 enhances the interaction between LC3 and ATG4 dependent on PI3K and triggers cellular autophagy. Strikingly, miR24-2 inhibits the degradation of pyruvate kinase M1 via autophagosome-P62 in hLCSCs. Furthermore, miR24-2 enhances the activity of Src by promoting the binding of PKM1 to the Src promoter regions in hLCSCs. In particular, our results also indicate that src gene determines the oncogenic functions of miR24-2. These results provided a valuable theoretical basis for the discovery of liver cancer therapeutic targets and diagnosis markers based on miR24-2.

Epidemiological characteristics of bacillary dysentery from 2009 to 2016 and its incidence prediction model based on meteorological factors.

BACKGROUND: This study aimed to analyse the epidemiological characteristics of bacillary dysentery (BD) caused by Shigella in Chongqing, China, and to establish incidence prediction models based on the correlation between meteorological factors and BD, thus providing a scientific basis for the prevention and control of BD. METHODS: In this study, descriptive methods were employed to investigate the epidemiological distribution of BD. The Boruta algorithm was used to estimate the correlation between meteorological factors and BD incidence. The genetic algorithm (GA) combined with support vector regression (SVR) was used to establish the prediction models for BD incidence. RESULTS: In total, 68,855 cases of BD were included. The incidence declined from 36.312/100,000 to 23.613/100,000, with an obvious seasonal peak from May to October. Males were more predisposed to the infection than females (the ratio was 1.118:1). Children < 5 years old comprised the highest incidence (295.892/100,000) among all age categories, and pre-education children comprised the highest proportion (34,658 cases, 50.335%) among all occupational categories. Eight important meteorological factors, including the highest temperature, average temperature, average air pressure, precipitation and sunshine, were correlated with the monthly incidence of BD. The obtained mean absolute percent error (MAPE), mean squared error (MSE) and squared correlation coefficient (R2) of GA_SVR_MONTH values were 0.087, 0.101 and 0.922, respectively. CONCLUSION: From 2009 to 2016, BD incidence in Chongqing was still high, especially in the main urban areas and among the male and pre-education children populations. Eight meteorological factors, including temperature, air pressure, precipitation and sunshine, were the most important correlative feature sets of BD incidence. Moreover, BD incidence prediction models based on meteorological factors had better prediction accuracies. The findings in this study could provide a panorama of BD in Chongqing and offer a useful approach for predicting the incidence of infectious disease. Furthermore, this information could be used to improve current interventions and public health planning.

miR­153 promotes neural differentiation in the mouse hippocampal HT­22 cell line and increases the expression of neuron­specific enolase.

MicroRNAs (miRNAs) have been found to play important regulatory roles in certain neurodegenerative diseases. The aim of the present study was to investigate the effect of miRNA­153 (miR­153) on the neural differentiation of HT­22 cells. Overexpression of miR­153 induced the differentiation of HT­22 cells, increasing the number of protrusions and branches, reducing the S phase distribution of the cell cycle, and attenuating the cell proliferation rate as determined using the Cell Counting Kit­8 assay. Furthermore, miR­153 increased the expression of neuron­specific γ­enolase (NSE), neuronal nuclei (NeuN), and N­ethylmaleimide­sensitive fusion attachment protein 23 (SNAP23) and SNAP25 at the transcriptional and protein level by PCR and western blot analysis. Moreover, miR­153 caused obvious upregulation of peroxiredoxin 5 (PRX5), which has been found to protect neural cells from death and apoptosis. miR­153 promoted neural differentiation and protected neural cells by upregulating the neuron markers γ­enolase, neuronal nuclei, and the functional proteins SNAP23, SNAP25 and PRX5. Therefore, miR­153 may be a potential target for the treatment of certain neurodegenerative diseases.

[The sedative effect of dexmedetomidine in outpatient undergoing dental surgery compared to several sedative drugs:a meta analysis].

PURPOSE: To evaluate the efficacy of dexmedetomidine and midazolam, ketamine or placebo administrated in outpatient dental surgery. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched from inception to October 2017,to find all randomized controlled trials(RCTs) about the sedative effect of dexmedetomidine versus midazolam, ketamine or placebo during outpatient dental surgery. The quality of the studies was evaluated by the method recommended by Cochrane collaboration. Meta analysis was conducted using Review Manager 5.3 software. RESULTS: Twelve clinical trials with 678 patients were included. The results of meta analysis showed that the sedation score of children was lower in group of dexmedetomidine than that of group of normal saline (SMD=-1.73,95%CI:-2.70～-0.77,P=0.0004) and the sedation score of adults was also lower in group of dexmedetomidine than that of group of normal saline(SMD=-2.23,95%CI:-4.39～-0.08,P=0.04).There was no significant difference in sedation satisfaction of children between dexmedetomidine and ketamine(RR=1.14,95%CI:1.00-1.30,P=0.05).Dexmedetomidine provided more satisfactory sedation of children than midazolam(RR=1.38,95%CI:1.15-1.67,P=0.0006),and there was no significant difference in sedation satisfaction of adults between dexmedetomidine and midazolam (RR=1.42,95%CI:0.86-2.33,P=0.17). Moreover,dexmedetomidine provided more satisfactory behavior of children than ketamine (RR=1.19,95%CI:1.03-1.36,P=0.01) and midazolam (RR=1.28,95%CI:1.07-1.54,P=0.008). CONCLUSIONS: Compared with other sedative drugs, dexmedetomidine may be a better choice for moderate sedation during outpatient dental surgery.

miR675 Accelerates Malignant Transformation of Mesenchymal Stem Cells by Blocking DNA Mismatch Repair.

miR675 is highly expressed in several human tumor tissues and positively regulates cell progression. Herein, we demonstrate that miR675 promotes malignant transformation of human mesenchymal stem cells. Mechanistically, we reveal that miR675 enhances the expression of the polyubiquitin-binding protein p62. Intriguingly, P62 competes with SETD2 to bind histone H3 and then significantly reduces SETD2-binding capacity to substrate histone H3, triggering drastically the reduction of three methylation on histone H3 36th lysine (H3K36me3). Thereby, the H3K36me3-hMSH6-SKP2 triplex complex is significantly decreased. Notably, the ternary complex's occupancy capacity on chromosome is absolutely reduced, preventing it from DNA damage repair. By virtue of the reductive degradation ability of SKP2 for aging histone H3.3 bound to mismatch DNA, the aging histone H3.3 repair is delayed. Therefore, the mismatch DNA escapes from repair, triggering the abnormal expression of several cell cycle-related genes and causing the malignant transformation of mesenchymal stem cells. These observations strongly suggest understanding the novel functions of miR675 will help in the development of novel therapeutic approaches in a broad range of cancer types.