Cell Journal (Yakhteh)最新文献

{"title":"CRISPR/Cas9-Mediated Generation of COL7A1-Deficient Keratinocyte Model of Recessive Dystrophic Epidermolysis Bullosa","authors":"Farzad Alipour, M. Ahmadraji, Elham Yektadoust, P. Mohammadi, H. Baharvand, M. Basiri","doi":"10.1101/2023.06.15.545036","DOIUrl":"https://doi.org/10.1101/2023.06.15.545036","url":null,"abstract":"Objective Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin fragility and ultimately lethal blistering disease caused by mutations in the COL7A1 gene which is responsible for coding type VII collagen. Investigating the pathological mechanisms and novel candidate therapies for RDEB could be fostered by new cellular models. Here, we developed multiple immortalized COL7A1-deficient keratinocyte cell lines using CRISPR/Cas9 technology as RDEB cellular model. Materials and Methods In this experimental study, we used transient transfection to express COL7A1-targeting gRNA and Cas9 in HEK001 immortalized keratinocyte cell line followed by enrichment with fluorescent-activated cell sorting (FACS) via GFP expressing cells (GFP+ HEK001). Homogenous single-cell clones were then isolated, genotyped, and evaluated for type VII collagen expression. We performed a scratch assay to confirm the functional effect of COL7A1 knockout. Results We achieved 46.1% (p < 0.001) efficiency of indel induction in the enriched transfected cell population. Except for 4% of single nucleotide insertions, the remaining indels were deletions of different sizes. Out of nine single clones expanded, two homozygous and two heterozygous COL7A1-deficient cell lines were obtained with defined mutation sequences. No off-target effect was detected in the knockout cell lines. Immunostaining and western blot analysis showed the lack of type VII collagen (COL7A1) protein expression in these cell lines. We also showed that COL7A1-deficient cells had higher motility compared with their wild-type counterparts. Conclusion We reported the first isogenic immortalized COL7A1-deficient keratinocyte lines that provide a useful cell culture model to investigate aspects of RDEB biology and potential therapeutic options.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80945948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Intraventricular Human Adipose-Derived Stem Cells Transplantation with Pregnenolone Treatment on Remyelination of Corpus Callosum in A Rat Model of Multiple Sclerosis","authors":"Mohammad Mardani, Raosul Ganji, N. Ghasemi, M. Kazemi, S. Razavi","doi":"10.22074/cellj.2022.8173","DOIUrl":"https://doi.org/10.22074/cellj.2022.8173","url":null,"abstract":"Objective Multiple sclerosis (MS) is known as a nerve tissue disorder, which causes demyelination of central nervous system (CNS) fibers. Cell-based treatment is a novel strategy for the treatment of demyelinating diseases such as MS. Adipose-derived stem cells (ADSCs) have neuroprotective and neuroregenerative effects and pregnenolone as a neurosteroid has remarkable roles in neurogenesis. We intend to examine the impact of intraventricular transplantation of human ADSCs and systemic injection of pregnenolone on the remyelination of a rat model cuprizone-induced demyelination. Materials and Methods This experimental study was performed on 36 male Wistar rats that received a regular diet and a cuprizone diet for 3 weeks for M.S. induction. Through lipoaspirate surgery, human-ADSCs (hADSCs) were obtained from a patient. Six groups of rats (n=6): healthy, MS, sham, pregnenolone injection, ADSCs transplantation, and pregnenolone injection/ADSCs transplantation were included in this study. For assessment of remyelination, transmission electron microscopy (TEM), immunohistochemistry staining, real-time reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were performed. Results TEM outcomes revealed an increase in the thickness of the fibers myelin in the treatment groups (P<0.05). We also observed a significant upregulation of MBP, PDGFR-α, and MOG after treatment with hADSCs and pregnenolone compared to other study groups (P<0.001). These results were confirmed by immunostaining analysis. Moreover, there was no significant difference between the ADSCs/pregnenolone group and the control group regarding the level of MBP, A2B5, and MOG proteins in ELISA. Conclusion Our data implied that the remyelination and cell recovery were more improved by intraventricular ADSCs transplantation and pregnenolone injection after inducing a rat model of MS.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86202531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant DNA Methylation Status and mRNA Expression Level of SMG1 Gene in Chronic Myeloid Leukemia: A Case-Control Study","authors":"Tahereh Hojjatipour, M. Sohani, Amirhosein Maali, S. Rostami, M. Azad","doi":"10.22074/cellj.2022.8526","DOIUrl":"https://doi.org/10.22074/cellj.2022.8526","url":null,"abstract":"Objective Chronic myeloid leukemia (CML) is a myeloproliferative malignancy with different stages. Aberrant epigenetic modifications, such as DNA methylation, have been introduced as a signature for diverse cancers which also plays a crucial role in CML pathogenesis and development. Suppressor with morphogenetic effect on genitalia (SMG1) gene recently has been brought to the spotlight as a potent tumor suppressor gene that can be suppressed by tumors for further progress. The present study aims to investigate SMG1 status in CML patients. Materials and Methods In this case-control study, peripheral blood from 30 patients with different phases of CML [new case (N)=10, complete molecular remission (CMR)=10, blastic phase (BP)=10] and 10 healthy subjects were collected. Methylation status and expression level of SMG1 gene promoter was assessed by methylation-specific polymerase chain reaction (MSP) and quantitative reverse-transcription PCR, respectively. Results MSP results of SMG1 gene promotor in the new case group were methylated (60% methylated, 30% hemimethylated and 10% unmethylated). All CMR and control group patients were unmethylated in the SMG1 gene promoter. In the BP group, methylated SMG1 promoter was seen (50% of patients had a methylated status and 50% had hemimethylated status). In comparison with the healthy subjects, expression level of SMG1 in the new case group was decreased (P<0.01); in the CMR group and BP-CML groups, it was increased (P<0.05). No significant correlation between patients’ hematological features and SMG1 methylation was seen. Conclusion Our results demonstrated that aberrant methylation of SMG1 occurred in CML patients and it had a significant association with SMG1 expression. SMG1 gene promoter showed diverse methylated status and subsequent expression levels in different phases of CML. These findings suggested possible participation of SMG1 suppression in the CML pathogenesis.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77861511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FHL1 Overexpression as A Inhibitor of Lung Cancer Cell Invasion via Increasing RhoGDIß mRNA Expression","authors":"Yanbo Zhang, Xuefeng Wang, Peng Wang, Xingle Zhang, Shangzhi Han, F. Huo","doi":"10.22074/cellj.2022.7763.","DOIUrl":"https://doi.org/10.22074/cellj.2022.7763.","url":null,"abstract":"Objective A lot of lncRNAs are implicated in oral squamous cell carcinoma (OSCC) progression. The study aimed at investigating lncRNA DS cell adhesion molecule antisense RNA 1 (DSCAM-AS1)’s functional role and molecular mechanism in OSCC. Materials and Methods In this experimental study, a total of 46 pairs of OSCC samples and para-cancerous tissues were collected during surgery. In OSCC tissues and cell lines, quantitative real time polymerase chain reaction (qRT- PCR) was performed for detecting DSCAM-AS1 and microRNA-138-5p (miR-138-5p) expression levels. Western blot was conducted to examine the enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) expression level. Then, DSCAM-AS1 was knocked down with siRNA in OSCC cells and MTT and EdU assays were conducted to evaluate OSCC cell proliferation. Transwell assay was utilized for detecting OSCC cell migration and invasion capacities. Besides, the relationships among DSCAM-AS1, miR-138-5p, and EZH2 were explored through RNA immunoprecipitation, dual-luciferase reporter assay, qRT-PCR, and Western blot. Results DSCAM-AS1 expression was remarkably increased in OSCC tissues and cell lines, and DSCAM-AS1 knockdown could significantly restrain OSCC cell proliferation, migration, and invasion. MiR-138-5p was identified as a target of DSCAM-AS1, and its inhibitor could reverse the suppressive effects of DSCAM-AS1 knockdown on OSCC progression. EZH2 was verified as a target of miR-138-5p, and EZH2 knockdown could counteract the promotional impact of miR-138-5p inhibitor on OSCC progression. Additionally, DSCAM-AS1, as a ceRNA, could regulate EZH2 expression via miR-138-5p. Conclusion DSCAM-AS1 can play a tumor-promoting role in OSCC via miR-138-5p/EZH2 axis.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80861105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP19A1 Promoters Activity in Human Granulosa Cells: A Comparison between PCOS and Normal Subjects","authors":"Zohreh Hashemain, Amir Amiri-Yekta, M. Khosravifar, Faezeh Alvandian, M. Shahhosseini, S. Hosseinkhani, P. Afsharian","doi":"10.22074/cellj.2022.7787","DOIUrl":"https://doi.org/10.22074/cellj.2022.7787","url":null,"abstract":"Objective Estrogen, a female hormone maintaining several critical functions in women's physiology, e.g., folliculogenesis and fertility, is predominantly produced by ovarian granulosa cells where aromatase enzyme converts androgen to estrogen. The principal enzyme responsible for this catalytic reaction is encoded by the CYP19A1 gene, with a long regulatory region. Abnormalities in this process cause metabolic disorders in women, one of the most common of which is polycystic ovary syndrome (PCOS). The main purpose of this research was to determine the effect of the promoters on aromatase expression in cells with normal and PCOS characteristics. Materials and Methods In this experimental study, four promoters of the CYP19A1 gene, including PII, I.3, I.4, and PII/ I .3 promoter fragments, were cloned upstream of the luciferase gene and transfected into normal and PCOS granulosa cells. Subsequently, the effect of follicle-stimulating hormone (FSH) on the activity of these regulatory regions was examined in the presence and absence of FSH. Western blotting was used to confirm aromatase expression in all groups. Data analysis was performed using ANOVA and paired sample t test, compared by post-hoc least significant difference (LSD) test. Results Luciferase results confirmed the intense activity of PII promoter in the presence of FSH. Moreover, the study demonstrated reduced activity of PII promoter in normal granulosa cells, possibly due to the regulatory region of I.3 next to PII. Conclusion FSH stimulates transcription of aromatase enzyme by affecting PII promoter, a process regulated by the inhibitory role of the I.3 region in PII activity in granulosa cells. Given the distinct role of these promoters in normal and PCOS granulosa cells, the importance of nuclear factors residing in these regions can be discerned.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78782574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation and Expression Status of The CpG-Island of SMG1 Promoter in Acute Myeloid Leukemia: A Follow-Up Study in Patients","authors":"Neda Karami, M. Ahmadi, S. Mohammadi, Amirhosein Maali, A. Alizadeh, Shaghayegh Pishkhan Dibazar, M. Azad","doi":"10.22074/cellj.2022.7798","DOIUrl":"https://doi.org/10.22074/cellj.2022.7798","url":null,"abstract":"Objective Aberrant alterations in DNA methylation are known as one of the hallmarks of oncogenesis and play a vital role in the progression of acute myeloid leukemia (AML). SMG1 is a member of the Phosphoinositide 3-kinases family, acting as a tumor suppressor gene. The aim of this study was the evaluation of the expression level and methylation status of SMG1 in AML. Materials and Methods In this follow-up study on AML patients admitted to Shariati Hospital, Tehran, Iran, the methylation status of SMG1 [performed by methylation-specific polymerase chain reaction (PCR)] and its expression level (performed by qRT-PCR) were evaluated in three phases: newly diagnosed, under treatment and complete remission. The correlation of the methylation status of SMG1, its expression level, and clinical/paraclinical data was analyzed by SPSS ver.25. Results This study on 18 patients and five control individuals showed that the CpG-islands of the SMG1 promoter in newly diagnosed cases is hypomethylated compared to the normal group (P=0.002) The fold change of SMG1 expression levels in new cases is 0.464 ± 0.468, while the fold change of SMG1 expression levels in under-treatment and in-remission patients is 0.973 ± 1.159 and 0.685 ± 0.885, respectively. In under-treatment patients, white blood cell (WBC) count decreases 114176.36 cell/µl with each unit of increase in fold change of SMG1 (P<0.0001), and Hb unit increases 2.062 g/dl with each unit of increase in fold change (P<0.0001) Also, in the remission phase, the Hb unit increases 1.395 g/dl with each unit increase in fold change (P=0.019). Conclusion The robust results of our study suggest that the methylation and expression of have a high impact on the pathogenesis of AML. Also, the methylation and expression of SMG1 can play a prognostic role in AML.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82625118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 and Endocrine System: A Cross-Sectional Study on 60 Patients with Endocrine Abnormality","authors":"Negin Hadisi, Hadi Abedi, M. Shokoohi, S. Taşdemir, Shahriyar Mamikhani, Shahla Meshgi, Arian Zolfagharzadeh, L. Roshangar","doi":"10.22074/cellj.2022.8079","DOIUrl":"https://doi.org/10.22074/cellj.2022.8079","url":null,"abstract":"Objective COVID-19 is an infectious disease that has become pandemic with a high mortality rate. This study aims to provide new insight into the relations between SARS-CoV-2 and the Endocrine system. Materials and Methods In this cross-sectional study, we have hospitalized 60 patients with a positive SARA-CoV-2 PCR test. The information of complete blood count and endocrine hormones was obtained when the patients were admitted to the hospital or for a maximum of 4 days onset the hospitalization. Results Of 60 patients with COVID-19, forty-four (73.33%) had at least one abnormality mean item >×3. In total, 26 (43.33%), 21 (35%), 18 (30%), 13 (21.67%), 31 (51.67%), 12 (20%), 30 (50%), 25 (41.67%) patients having estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, testosterone, cortisol and thyroid stimulating hormone (TSH) abnormal test results, respectively. There was no change in creatinine levels. FSH has shown drastic changes in both sexes’ intensity (F: 769, P<0.0001). Although TSH had many abnormalities in women, analysis has shown no significant P value (P=0.4558). Furthermore, prolactin and testosterone mean level in men and the estradiol mean level in women have shown no significant P value (P=0.2077, P=0.1446, P=0.1351, respectively). Conclusion Results suggest that COVID-19 affects directly or non-directly glands and related hormones.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90802773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effect of the HASPIN Inhibitor CHR-6494 on BxPC-3-Luc, A Luciferase-Expressing Pancreatic Cancer Cell Line","authors":"Hiromitsu Tanaka, Hisayo Nishida-Fukuda, M. Wada, K. Tokuhiro, Hiroaki Matsushita, Y. Ando","doi":"10.22074/cellj.2022.7796","DOIUrl":"https://doi.org/10.22074/cellj.2022.7796","url":null,"abstract":"HASPIN acts in chromosome segregation via histone phosphorylation. Recently, HASPIN inhibitors have been shown to suppress growth of various cancer cells. Pancreatic cancer has no symptom in the early stages and may progress before detection. So, the 5-year survival rate is low. Here, we reported that administration of the HASPIN inhibitor, CHR-6494, to mice bearing pancreatic BxPC-3-Luc cancer cells significantly suppressed growth of BxPC-3-Luc cells. CHR-6494 might be a useful agent for treating pancreatic cancer.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80747582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of MAT2A-Related Methionine Metabolism Enhances The Efficacy of Cisplatin on Cisplatin-Resistant Cells in Lung Cancer","authors":"Xiaoya Zhao, Lude Wang, Hai-Fei Lin, Jing Wang, Jianfei Fu, D. Zhu, Wenxia Xu","doi":"10.22074/cellj.2022.7907","DOIUrl":"https://doi.org/10.22074/cellj.2022.7907","url":null,"abstract":"Objective Tumor drug resistance is a vital obstacle to chemotherapy in lung cancer. Methionine adenosyltransferase 2A has been considered as a potential target for lung cancer treatment because targeting it can disrupt the tumorigenicity of lung tumor-initiating cells. In this study, we primarily observed the role of methionine metabolism in cisplatin-resistant lung cancer cells and the functional mechanism of MAT2A related to cisplatin resistance. Materials and Methods In this experimental study, we assessed the half maximal inhibitory concentration (IC50) of cisplatin in different cell lines and cell viability via Cell Counting Kit-8. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of relative proteins and genes. Crystal violet staining was used to investigate cell proliferation. Additionally, we explored the transcriptional changes in lung cancer cells via RNA-seq. Results We found H460/DDP and PC-9 cells were more resistant to cisplatin than H460, and MAT2A was overexpressed in cisplatin-resistant cells. Interestingly, methionine deficiency enhanced the inhibitory effect of cisplatin on cell activity and the pro-apoptotic effect. Targeting MAT2A not only restrained cell viability and proliferation, but also contributed to sensitivity of H460/DDP to cisplatin. Furthermore, 4283 up-regulated and 5841 down-regulated genes were detected in H460/DDP compared with H460, and 71 signal pathways were significantly enriched. After treating H460/DDP cells with PF9366, 326 genes were up-regulated, 1093 genes were down-regulated, and 13 signaling pathways were significantly enriched. In TNF signaling pathway, CAS7 and CAS8 were decreased in H460/DDP cells, which increased by PF9366 treatment. Finally, the global histone methylation (H3K4me3, H3K9me2, H3K27me3, H3K36me3) was reduced under methionine deficiency conditions, while H3K9me2 and H3K36me3 were decreased specially via PF9366. Conclusion Methionine deficiency or MAT2A inhibition may modulate genes expression associated with apoptosis, DNA repair and TNF signaling pathways by regulating histone methylation, thus promoting the sensitivity of lung cancer cells to cisplatin.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88634949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-205 Reverses MDR-1 Mediated Doxorubicin Resistance via PTEN in Human Liver Cancer HepG2 Cells","authors":"Mei Li, Zhubin Li, J. Song, Xu Li, Peng-Fei Zhai, Xu‐Peng Mu, Fa-qi Qiu, L. Yao","doi":"10.22074/cellj.2022.7231","DOIUrl":"https://doi.org/10.22074/cellj.2022.7231","url":null,"abstract":"Objective The aim of the recent study was to investigate the effects of miR-205 on reversing Doxorubicin (DOX) resistance, as chemotherapeutic agents through up-regulation of PTEN in human liver cancer HepG2 cells. Materials and Methods In this experimental study, the drug resistance in liver cancer cells via drug efflux inhibition and enhancing apoptosis by the regulation of PTEN and multi-drug resistance/ P-glycoprotein (MDR/P-gp) expression was revealed. Using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, effect of DOX on cell proliferation was evaluated after miR-205 transfection in HepG2 and HepG2/DOX cells. Activity of P-gp on drug efflux was measured by the Rhodamine 123 (Rho-123) assay. PTEN mRNA expression levels were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry was used to measure the apoptotic ratio of HepG2/DOX cells. Results miR-205 overexpression considerably inhibited the HepG2/DOX cells viability (P<0.05). qRT-PCR results revealed that PTEN is a pivotal regulator in PI3K/Akt/P-gp axis. Overexpression miR-205 resulted in up-regulation PTEN and ultimately down-regulation of P-gp. This inhibits drug resistance, proliferation and induces apoptosis in HepG2/DOX cells (P<0.05). Whilst, treatment with 10 μM of special inhibitors, including LY294002 (PI3K) or PD098059 (MAPK), increased Rho 123-associated MFI, treatment with 10 μM of SF1670 (PTEN) almost abolished the effect of miR-205 overexpression (P<0.05). Finally, we found that miR-205 was down-regulated in HepG2/DOX cells, and its overexpression led to enhancing apoptosis with re-sensitization of HepG2/DOX cell lines to DOX through PTEN/PI3K/ Akt/MDR1 pathway. Conclusion These findings may introduce miR-205 as a predictive biomarker and a potential treatment target for liver cancer therapy during MDR.","PeriodicalId":9692,"journal":{"name":"Cell Journal (Yakhteh)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77188076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}