SATB2 targeted by methylated miR‐34c‐5p suppresses proliferation and metastasis attenuating the epithelial‐mesenchymal transition in colorectal cancer

Objectives

SATB2 has been shown to be markedly reduced in colorectal cancer (CRC) tissues relative to paired normal controls; however, the mechanism behind remains not well understood. To investigate why SATB2 was down‐regulated in CRC, we attempted to analyse it from the angle of miRNA‐mRNA modulation.

Materials and methods

SATB2 expression was detected in CRC tissues using immunohistochemistry and verified using real‐time PCR on mRNA level, followed by analysis of clinicopathological significance of its expression. Metastatic variation of CRC cells was evaluated both in vivo and in vitro. To find out the potential miRNA that directly regulate the SATB2, luciferase reporter assay was performed following the bioinformatic prediction.

Results

SATB2 was confirmed to be closely linked with the metastasis and shorter overall survival of CRC in our own cases. Silencing of SATB2 was shown to be able to promote the metastatic ability of CRC cells in vivo, enhancing the epithelial‐mesenchymal transition (EMT). Mechanistically, miR‐34c‐5p was identified to be a novel miRNA that can directly modulate the SATB2. It turned out that the promoter of miR‐34c‐5p was methylated, which leads to the repression of miR‐34c‐5p in CRC. Treatment with 5‐Aza‐dC can reasonably and significantly restore the level of miR‐34c‐5p in CRC cells relative to control, thereby down‐regulating the SATB2.

Conclusions

Together, our study revealed that SATB2 targeted by methylated miR‐34c‐5p can suppress the metastasis, weakening the EMT in CRC.

     

Loss of PPM1F expression predicts tumour recurrence and is negatively regulated by miR‐590‐3p in gastric cancer

Objectives

MicroRNAs (miRNAs) as small non‐coding RNA molecules act by negatively regulating their target genes. Recent studies have shown that protein phosphatase Mg2+/Mn2+‐dependent 1F (PPM1F) plays a critical role in cancer metastasis. But, the regulation mechanisms of PPM1F by miRNAs in gastric cancer (GC) remain undefined.

Methods

The correlation of PPM1F or miR‐590‐3p (miR‐590) expression with clinicopathological features and prognosis of the patients with GC was analysed by TCGA RNA‐sequencing data. The miRNAs that target PPM1F gene were identified by bioinformatics and Spearman correlation analysis, and the binding site between miR‐590 and PPM1F 3′UTR was confirmed by dual luciferase assay. MTT and Transwell assays were conducted to evaluate the effects of miR‐590 or (and) PPM1F on cell proliferation and invasion.

Results

We found that PPM1F expression was downregulated in GC tissues and cell lines and was correlated with tumour recurrence in patients with GC. The decreased expression of PPM1F was attributed to the dysregulation of miR‐590 expression rather than its genetic or epigenetic alterations. Overexpression of miR‐590 promoted cell proliferation and invasion capability of GC cells, while knockdown of miR‐590 reversed these effects. Moreover, PPM1F was validated as a direct target of miR‐590 and counteracted the tumour‐promoting effects caused by miR‐590. The expression of miR‐590 presented the negative correlation with PPM1F expression and acted as an independent prognostic factor for tumour recurrence in patients with GC.

Conclusion

PPM1F may function as a suppressive factor and is negatively regulated by miR‐590 in GC.

     

Schisandrin B down‐regulated lncRNA BCYRN1 expression of airway smooth muscle cells by improving miR‐150 expression to inhibit the proliferation and migration of ASMC in asthmatic rats

Objective

The mechanism of Schisandrin B on the proliferation and migration of airway smooth muscle cells (ASMCs) in asthmatic rats was explored.

Methods

SD rats were divided into three groups: control (group 1), model (group 2) and model + Schisandrin B (group 3). miR‐150 and lncRNA BCYRN1 levels were measured by qRT‐PCR. The combination of BCYRN1 and miR‐150 was detected by RNA pull down. ASMCs’ viability/proliferation/migration were examined by WST‐1 assay and 24‐well Transwell system.

Results

Schisandrin B up‐regulated miR‐150 expression and down‐regulated BCYRN1 expression in sensitized rats. Schisandrin B reversed the expression of miR‐150 and BCYRN1 in MV‐treated ASMCs. In addition, Schisandrin B inhibited the viability, proliferation and migration of MV‐induced ASMCs. We also found miR‐150 inhibited BCYRN1 expression which was proved by experiments using ASMCs transfected with miR‐150 inhibitor.

Conclusion

Schisandrin B increased miR‐150 expression and decreased BCYRN1, and BCYRN1 expression was inhibited by miR‐150, which indicated that Schisandrin B could regulate BCYRN1 through miR‐150.

     

Loss‐of‐function of miR‐142 by hypermethylation promotes TGF‐β‐mediated tumour growth and metastasis in hepatocellular carcinoma

Objectives

Hypermethylation‐induced epigenetic silencing of tumour suppressor genes (TSGs) are frequent events during carcinogenesis. MicroRNA‐142 (miR‐142) is found to be dysregulated in cancer patients to participate into tumour growth, metastasis and angiogenesis. However, the tumour suppressive role of miR‐142 and the status of methylation are not fully understood in hepatocellular carcinoma (HCC).

Methods

Hepatocellular carcinoma tissues and corresponding non‐neoplastic tissues were collected. The expression and function of miR‐142 and TGF‐β in two HCC cell lines were determined. The miRNA‐mRNA network of miR‐142 was analysed in HCC cell lines.

Results

We found that the miR‐142 expression was reduced in tumour tissues and two HCC cell lines HepG2 and SMMC7721, which correlated to higher TNM stage, metastasis and differentiation. Moreover, miR‐142 was identified to directly target and inhibit transforming growth factor β (TGF‐β), leading to decreased cell vitality, proliferation, EMT and the ability of pro‐angiogenesis in TGF‐β‐dependent manner. Interestingly, the status of methylation of miR‐142 was analysed and the results found the hypermethylated miR‐142 in tumour patients and cell lines. The treatment of methylation inhibitor 5‐Aza could restore the expression of miR‐142 to suppress the TGF‐β expression, which impaired TGF‐β‐induced tumour growth.

Conclusion

These findings implicated that miR‐142 was a tumour suppressor gene in HCC and often hyermethylated to increase TGF‐β‐induced development of hepatocellular carcinoma.

     

miR‐34c works downstream of p53 leading to dairy goat male germline stem‐cell (mGSCs) apoptosis

Objectives

Recent lines of evidence have indicated that miR‐34c can play important roles in regulation of the cell cycle, cell senescence and apoptosis of mouse and human tumour cells, spermatogenesis, and male germ‐cell apoptosis. However, there is little information on the effects of miR‐34c on proliferation and apoptosis of livestock male germ cells. The dairy goat is a convenient domestic species for biological investigation and application. The purpose of this study was to investigate the effects of miR‐34c on apoptosis and proliferation of dairy goat male germline stem cells (mGSCs), as well as to determine the relationship between p53 and miR‐34c in this species.

Materials and methods

Morphological observation, miRNA in situ hybridisation (ISH), bromodeoxyuridine staining, flow cytometry, quantitative‐RT‐PCR (Q‐RT‐PCR) and western blotting were utilized to ascertain apoptosis and proliferation of mGSCs, through transfection of miR‐34c mimics (miR‐34c), miR‐34c inhibitor (anti‐miR‐34c), miR‐34c mimics and inhibitors co‐transfected (mixture) compared to control groups.

Results

Results manifested that miR‐34c over‐expression promoted mGSCs apoptosis and suppressed their proliferation. Simultaneously, a variety of apoptosis‐related gene expression was increased while some proliferation‐related genes were downregulated. Accordingly, miR‐34c promoted apoptosis in mGSCs and reduced their proliferation; moreover, expression of miR‐34c was p53‐dependent.

Conclusions

This study is the first to provide a model for study of miRNAs and mechanisms of proliferation and apoptosis in male dairy goat germ cells.

     

Long non‐coding RNA LOC554202 modulates chordoma cell proliferation and invasion by recruiting EZH2 and regulating miR‐31 expression

Objectives

Chordoma is a rare malignant bone tumour arising from notochordal remnants. Long non‐coding RNA LOC554202, as the host gene of miR‐31, contributes to various cancer developments. However, little is known about the biological function of LOC554202 in chordoma. Here, the relationship between LncRNA LOC554202, miR‐31 and EZH2 was elucidated in chordoma.

Materials and methods

The levels of LOC554402, miR‐31, EZH2, RNF144B, and epithelial‐mesenchymal transition (EMT) markers were measured in chordoma tissues and the chordoma cell lines via quantitative real‐time PCR (qRT‐PCR) or Western blot. FISH assay demonstrated the LOC554402 expression in chordoma tissues. The chordoma cell lines, U‐CH1 and JHC7, were transfected with siRNA or miRNA mimics and analysed for cell proliferation ability, apoptosis, cell migration, and invasion. RNA pull down, RIP assay, and Luciferase Reporter Assay were used to analyze the interaction between LOC554202 and EZH2. Animal tumour xenografts were generated, and qRT‐PCR was performed to investigate EZH2, miR‐31, and RNB144B expression on tumour growth in vivo.

Results

We found elevated expression of LOC554202 was associated with a decreased level of miR‐31 in cancer tissues. Knockdown of LOC554202 or overexpression of miR‐31 suppressed the proliferation, migration, and invasion of chordoma cells. Unexpectedly, EZH2 as a binding protein of LOC554202, and it was positively regulated by LOC554202, leading to the reduced expression of miR‐31. Furthermore, the impaired function of miR‐31 restored expression of the oncogene RNF144B and maintained the metastasis‐promoting activity in vitro. The results in vivo confirmed the anti‐tumour effects of knockdown of LOC554202, which inhibited EZH2/miR‐31 to activate the oncogene RNF144B.

Conclusion

Our results suggest that LOC554202 may play an important role in the progression of chordoma by the direct upregulation of EZH2 and indirect promotion of RNF144B via miR‐31.

     

Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA‐4295 that activates CDKN1A

Objectives

Ginsenoside Rh2 (GRh2) has demonstrative therapeutic effects on a variety of diseases, including some tumours. However, the effects of GRh2 on prostate cancer (PC) cell growth remain unknown, and were, thus, addressed in the present study.

Materials and methods

PC3 and DU145 PC cell lines were exposed to GRh2. Cell proliferation was assessed in an MTT assay and by BrdU incorporation. Apoptosis of the cells were assessed by TUNEL staining. Total RNA was assessed by RT‐qPCR. Protein levels were assessed by Western blotting. Bioinformatics and dual luciferase reporter assay were applied to determine the functional binding of miRNA to mRNA of target gene.

Results

GRh2 dose‐dependently decreased PC cell proliferation, but did not alter cell apoptosis. Mechanistically, GRh2 dose‐dependently increased the protein, but not mRNA of a cell‐cycle suppressor CDKN1A in PC cells, suggesting the presence of microRNA (miRNA)‐mediated protein translation control of CDKN1A by GRh2. In all candidate miRNAs that bind to 3′‐UTR of CDKN1A, miR‐4295 was specifically found to be suppressed dose‐dependently by GRh2 in PC cells. Moreover, miR‐4295 bound CDKN1A to suppress its protein translation. Furthermore, cell proliferation in PC cells that overexpressed miR‐4295 did not alter in response to GRh2.

Conclusions

GRh2 may inhibit PC cell growth through suppression of microRNA‐4295 that activates CDKN1A.

     

The inhibitory effects of capillarisin on cell proliferation and invasion of prostate carcinoma cells

Objectives

Capillarisin (Cap), an active component of Artemisia capillaris root extracts, is characterized by its anti‐inflammatory, anti‐oxidant and anti‐cancer properties. Nevertheless, the functions of Cap in prostate cancer have not been fully explored. We evaluated the potential actions of Cap on the cell proliferation, migration and invasion of prostate carcinoma cells.

Materials and methods

Cell proliferation and cell cycle distribution were measured by water‐soluble tetrazolium‐1 and flow cytometry assays. The expression of cyclins, p21, p27, survivin, matrix metallopeptidase (MMP2 and MMP9) were assessed by immunoblotting assays. Effects of Cap on invasion and migration were determined by wound closure and matrigel transmigration assays. The constitutive and interlukin‐6 (IL‐6)‐inducible STAT3 activation of prostate carcinoma cells were determined by immunoblotting and reporter assays.

Results

Capillarisin inhibited androgen‐independent DU145 and androgen‐dependent LNCaP cell growth through the induction of cell cycle arrest at the G0/G1 phase by upregulating p21 and p27 while downregulating expression of cyclin D1, cyclin A and cyclin B. Cap decreased protein expression of survivin, MMP‐2, and MMP‐9 and therefore blocked the migration and invasion of DU145 cells. Cap suppressed constitutive and IL‐6‐inducible STAT3 activation in DU145 and LNCaP cells.

Conclusions

Our data indicate that Cap blocked cell growth by modulation of p21, p27 and cyclins. The inhibitory effects of Cap on survivin, MMP‐2, MMP‐9 and STAT3 activation may account for the suppression of invasion in prostate carcinoma cells. Our data suggest that Cap might be a therapeutic agent in treating advanced prostate cancer with constitutive STAT3 or IL‐6‐inducible STAT3 activation.

     

Low‐intensity pulsed ultrasound induced enhanced adipogenesis of adipose‐derived stem cells

Objective

The aim of this study was to investigate effects of low‐intensity pulsed ultrasound (LIPUS) on differentiation of adipose‐derived stem cells (ASCs), in vitro.

Materials and methods

Murine ASCs were treated with LIPUS for either three or five days, immediately after adipogenic induction, or delayed for 2 days. Expression of adipogenic genes PPAR‐γ1, and APN, was examined by real‐time PCR. Immunofluorescence (IF) staining was performed to test for PPAR‐γ at the protein level.

Results

Our data revealed that specific patterns of LIPUS up‐regulated levels of both PPAR‐γ1 and APN mRNA, and PPAR‐γ protein.

Conclusions

In culture medium containing adipogenic reagents, LIPUS enhanced ASC adipogenesis.

     

FBXW7 suppresses epithelial‐mesenchymal transition and chemo‐resistance of non‐small‐cell lung cancer cells by targeting snai1 for ubiquitin‐dependent degradation

Objectives

FBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin‐mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear.

Materials and Methods

Immunohistochemical staining and qRT‐PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour‐adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere‐formation assays. Immunofluorescence and co‐immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW7.

Results

We detected the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW7 expression tend to have both poorer 5‐year survival outcomes, and shorter disease‐free survival, comparing to those with higher FBXW7 levels. Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo‐sensitivity and inhibiting Epithelial‐mesenchymal Transition (EMT) progress. Results further showed that FBXW7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC, which could be partially abrogated by restoring Snai1 expression.

Conclusions

FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC

     

Overexpression of hCLP46 enhances Notch activation and regulates cell proliferation in a cell type‐dependent manner

Objectives

Human CAP10‐like protein 46 kDa (hCLP46), also known as Poglut1, has been shown to be an essential regulator of Notch signalling. hCLP46 is overexpressed in primary acute myelogenous leukaemia, T‐acute lymphoblastic leukaemia samples and other leukaemia cell lines. However, effects of hCLP46 overexpression, up to now, have remained unknown.

Materials and methods

In this study, we established stable 293TRex cell lines inducibly overexpressing hCLP46, and knocked down hCLP6 with a specific small interfering RNA to explore function of the protein in Notch signalling and cell proliferation.

Results

hCLP46 overexpression enhanced Notch1 activation in 293Trex cells in a ligand‐dependent manner, with increased Notch signalling enhancing Hes1 expression. We further verified that overexpression of hCLP46 inhibited proliferation of 293TRexs and was correlated with increases in cyclin dependent kinase inhibitors p21 and p27, whereas reduced hCLP46 expression moderately increased cell proliferation. In addition, p21 and p27 protein levels were higher when Notch signalling was activated by EDTA treatment.

Conclusions

Taken together, hCLP46 enhanced Notch activation and inhibited 293TRex cell proliferation through CDKI signalling.

     

Fluoxetine induces autophagic cell death via eEF2K‐AMPK‐mTOR‐ULK complex axis in triple negative breast cancer

Objectives

Triple negative breast cancer (TNBC) is a complex and intrinsically aggressive tumour with poor prognosis, and the discovery of targeted small‐molecule drugs for TNBC treatment still remains in its infancy. In this study, we aimed to discover a small‐molecule agent for TNBC treatment and illuminate its potential mechanisms.

Materials and methods

Cell viability was detected by using methylthiazoltetrazolium (MTT) assay. Electron microscopy, GFP‐LC3 transfection, monodansylcadaverine staining and apoptosis assay were performed to determine Fluoxetine‐induced autophagy and apoptosis. Western blotting and siRNA transfection were carried out to investigate the mechanisms of Fluoxetine‐induced autophagy. iTRAQ‐based proteomics analysis was used to explore the underlying mechanisms.

Results

We have demonstrated that Fluoxetine had remarkable anti‐proliferative activities and induced autophagic cell death in MDA‐MB‐231 and MDA‐MB‐436 cells. The mechanism for Fluoxetine‐induced autophagic cell death was associated with inhibition of eEF2K and activation of AMPK‐mTOR‐ULK complex axis. Further iTRAQ‐based proteomics and network analyses revealed that Fluoxetine‐induced mechanism was involved in BIRC6, BNIP1, SNAP29 and Bif‐1.

Conclusions

These results demonstrate that Fluoxetine induces apoptosis and autophagic cell death in TNBC, which will hold a promise for the future TNBC therapy.

     

Long non‐coding RNA FAL1 functions as a ceRNA to antagonize the effect of miR‐637 on the down‐regulation of AKT1 in Hirschsprung's disease

Objectives

Emerged evidence demonstrates that long non‐coding RNAs (lncRNAs) may play quintessential regulatory roles in the cellular processes, tumourigenesis and the development of disease. Though focally amplified lncRNA on chromosome 1 (FAL1) has been identified to have crucial functions in many diseases, its biological mechanism in the development of Hirschsprung's disease (HSCR) still remains unknown.

Materials and methods

The expression levels of FAL1 in HSCR aganglionic tissues and matched normal specimens were detected by quantitative real‐time PCR (qRT‐PCR). Cell proliferation and migration were detected by Cell Counting Kit‐8 (CCK‐8) assay, Ethynyl‐deoxyuridine (EdU) assay and transwell assay relatively. Cell cycle and apoptosis were assessed using flow cytometer analysis. Moreover, the novel targets of FAL1 were confirmed with the help of bioinformatics analysis and dual‐luciferase reporter assay. Western blot assay as well as RNA immunoprecipitation (RIP) assay was conducted to investigate the potential mechanism.

Results

FAL1 expression was markedly down‐regulated in HSCR aganglionic tissues and decreased FAL1 expression was associated with the diagnosis of HSCR. Cell functional analyses indicated that FAL1 overexpressing notably promoted cell proliferation and migration, while down‐regulation of FAL1 suppressed cell proliferation and migration. Additionally, Flow cytometry assay demonstrated that knockdown of FAL1 induced markedly cell cycle stalled in the G0/G1 phase. Furthermore, FAL1 could positively regulate AKT1 expression by competitively binding to miR‐637.

Conclusions

These results illuminated that FAL1 may work as a ceRNA to modulate AKT1 expression via competitively binding to miR‐637 in HSCR, suggesting that it may be clinically valuable as a biomarker of HSCR.

     

Oroxylin A inhibits ethanol‐induced hepatocyte senescence via YAP pathway

Objectives

Oroxylin A, a natural flavonoid isolated from Scutellaria baicalensis, has been reported to have anti‐hepatic injury effects. However, the effects of oroxylin A on alcoholic liver disease (ALD) remains unclear. The aim of this study was to elucidate the effects of oroxylin A on ALD and the potential mechanisms.

Materials and methods

Male ICR mice and human hepatocyte cell line LO₂ were used. Yes‐associated protein (YAP) overexpression and knockdown were achieved using plasmid and siRNA technique. Cellular senescence was assessed by analyses of the senescence‐associated β‐galactosidase (SA‐β‐gal), senescence marker p16, p21, Hmga1, cell cycle and telomerase activity.

Results

Oroxylin A alleviated ethanol‐induced hepatocyte damage by suppressing activities of supernatant marker enzymes. We found that oroxylin A inhibited ethanol‐induced hepatocyte senescence by decreasing the number of SA‐β‐gal‐positive LO₂ cells and reducing the expression of senescence markers p16, p21 and Hmga1 in vitro. Moreover, oroxylin A affected the cell cycle and telomerase activity. Of importance, we revealed that YAP pharmacological inhibitor verteporfin or YAP siRNA eliminated the effect of oroxylin A on ethanol‐induced hepatocyte senescence in vitro, and this was further supported by the evidence in vivo experiments.

Conclusion

Therefore, these aggregated data suggested that oroxylin A relieved alcoholic liver injury possibly by inhibiting the senescence of hepatocyte, which was dependent on its activation of YAP in hepatocytes.

     

Galantamine inhibits β‐amyloid‐induced cytostatic autophagy in PC12 cells through decreasing ROS production

Objectives

Alzheimer's disease (AD) is one of the most prevalent brain diseases among the elderly, majority of which is caused by abnormal deposition of amyloid beta‐peptide (Aβ). Galantamine, currently the first‐line drug in treatment of AD, has been shown to diminish Aβ‐induced neurotoxicity and exert favourable neuroprotective effects, but the detail mechanisms remain unclear.

Materials and methods

Effects of galantamine on Aβ‐induced cytotoxicity were checked by MTT, clone formation and apoptosis assays. The protein variations and reactive oxygen species (ROS) production were measured by western blotting analysis and dichloro‐dihydro‐fluorescein diacetate assay, respectively.

Results

Galantamine reversed Aβ‐induced cell growth inhibition and apoptosis in neuron cells PC12. Aβ activated the entire autophagy flux and accumulation of autophagosomes, and the inhibition of autophagy decreased the protein level of cleaved‐caspase‐3 and Aβ‐induced cytotoxicity. Meanwhile, galantamine suppressed Aβ‐mediated autophagy flux and accumulation of autophagosomes. Moreover, Aβ upregulated ROS accumulation, while ROS scavengers N‐acetyl‐l ‐cysteine impaired Aβ‐mediated autophagy. Further investigation showed that galantamine downregulated NOX4 expression to inhibit Aβ‐mediated ROS accumulation and autophagy.

Conclusions

Galantamine inhibits Aβ‐induced cytostatic autophagy through decreasing ROS accumulation, providing new insights into deep understanding of AD progression and molecular basis of galantamine in neuroprotection.

     

KDM6A promotes chondrogenic differentiation of periodontal ligament stem cells by demethylation of SOX9

Objectives

KDM6A has been demonstrated critical in the regulation of cell fates. However, whether KDM6A is involved in cartilage formation remains unclear. In this study, we investigated the role of KDM6A in chondrogenic differentiation of PDLSCs, as well as the underlying epigenetic mechanisms.

Methods

KDM6A shRNA was transfected into PDLSCs by lentivirus. The chondrogenic differentiation potential of PDLSCs was assessed by Alcian blue staining. Immunofluorescence was performed to demonstrate H3K27me3 and H3K4me3 levels during chondrogenesis. SOX9, Col2a1, ACAN and miRNAs (miR‐29a, miR‐204, miR‐211) were detected by real‐time RT‐PCR. Western blot was performed to evaluate SOX9, H3K27me3 and H3K4me3.

Results

The production of proteoglycans in PDLSCs was decreased after knockdown of KDM6A. Depletion of KDM6A inhibited the expression of SOX9, Col2a1, ACAN and resulted in increased H3K27me3 and decreased H3K4me3 levels. EZH2 inhibitor rescued the chondrogenic potential of PDLSCs after knockdown of KDM6A by regulating H3K27me3. Additionally, miR‐29a, miR‐204 and miR‐211 were also involved in the process of PDLSCs chondrogenesis.

Conclusions

KDM6A is required in chondrogenic differentiation of PDLSCs by demethylation of H3K27me3, and EZH2 inhibitor could rescue chondrogenesis of PDLSCs after knockdown of KDM6A. It could be inferred that upregulation of KDM6A or application of EZH2 inhibitor might improve mesenchymal stem cell mediated cartilage regeneration in inflammatory tissue destruction such as osteoarthritis.