BMC Molecular and Cell Biology最新文献

{"title":"Exogenous 8-hydroxydeoxyguanosine attenuates doxorubicin-induced cardiotoxicity by decreasing pyroptosis in H9c2 cardiomyocytes.","authors":"Soyoung Hwang,&nbsp;Se-Hee Kim,&nbsp;Kwai Han Yoo,&nbsp;Myung-Hee Chung,&nbsp;Jin Woo Lee,&nbsp;Kuk Hui Son","doi":"10.1186/s12860-022-00454-1","DOIUrl":"https://doi.org/10.1186/s12860-022-00454-1","url":null,"abstract":"<p><p>Doxorubicin (DOX), which is widely used in cancer treatment, can induce cardiomyopathy. One of the main mechanisms whereby DOX induces cardiotoxicity involves pyroptosis through the NLR family pyrin domain containing 3 (NLRP3) inflammasome and gasdermin D (GSDMD). Increased NAPDH oxidase (NOX) and oxidative stress trigger pyroptosis. Exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases reactive oxygen species (ROS) production by inactivating NOX. Here, we examined whether 8-OHdG treatment can attenuate DOX-induced pyroptosis in H9c2 cardiomyocytes. Exposure to DOX increased the peroxidative glutathione redox status and NOX1/2/4, toll-like receptor (TLR)2/4, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while an additional 8-OHdG treatment attenuated these effects. Furthermore, DOX induced higher expression of NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a c-terminal caspase recruitment domain (ASC), and pro-caspase-1. Moreover, it increased caspase-1 activity, a marker of pyroptosis, and interleukin (IL)-1β expression. All these effects were attenuated by 8-OHdG treatment. In addition, the expression of the cardiotoxicity markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was increased by DOX, whereas the increase of ANP and BNP induced by DOX treatment was reversed by 8-OHdG. In conclusion, exogenous 8-OHdG attenuated DOX-induced pyroptosis by decreasing the expression of NOX1/2/3, TLR2/4, and NF-κB. Thus, 8-OHdG may attenuate DOX-induced cardiotoxicity through the inhibition of pyroptosis.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"55"},"PeriodicalIF":2.8,"publicationDate":"2022-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9753270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10360718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of adhesion of thawed and cultured synovial mesenchymal stem cells to the porcine meniscus and the relevance of cell surface microspikes.","authors":"Shunichi Fujii,&nbsp;Kentaro Endo,&nbsp;Nobutake Ozeki,&nbsp;Yuriko Sakamaki,&nbsp;Yuji Kohno,&nbsp;Mitsuru Mizuno,&nbsp;Hisako Katano,&nbsp;Kunikazu Tsuji,&nbsp;Hideyuki Koga,&nbsp;Ichiro Sekiya","doi":"10.1186/s12860-022-00456-z","DOIUrl":"https://doi.org/10.1186/s12860-022-00456-z","url":null,"abstract":"<p><strong>Background: </strong>Placement of a cultured synovial mesenchymal stem cell (MSC) suspension on a repaired meniscus for 10 min accelerated meniscus repair. Upon placement of the MSC suspension on the meniscus, microspikes projecting from the MSC surface trap meniscus fibers and promote MSC adhesion. Thawed cryopreserved MSCs are preferred materials for meniscus repair, as they can be transplanted without additional culture. However, the adhesion ability of thawed cryopreserved MSCs is unknown. Here, we compared the proportion of cultured versus thawed MSCs adhering to a porcine meniscus immediately and 10 min after placement. We also investigated the relationship between adhesion and the number of microspikes on the synovial MSCs.</p><p><strong>Methods: </strong>Synovial MSCs were prepared from the knees of four donors with osteoarthritis. The \"cultured MSCs\" were thawed MSCs that were re-cultured and suspended in PBS for transplantation. A similarly prepared suspension was cryopreserved, thawed again, suspended in PBS, and used without further culture as the \"thawed MSCs.\" MSCs with at least three microspikes in SEM images were defined as microspike-positive MSCs. Porcine meniscus surfaces were abraded, cut into a cylindrical shape, and treated with MSC suspension. Non-adherent cells were counted immediately and again 10 min after placement to calculate the adhesion proportion.</p><p><strong>Results: </strong>The proportion of microspike-positive MSCs was significantly higher in thawed (53 ± 3%) than in cultured (28 ± 5%) MSC suspensions. MSC adhesion to the meniscus was significantly better for the thawed than for the cultured MSC suspensions immediately after placement on the meniscus, but no differences were detected after 10 min. The proportion of MSCs with microspikes in the cell suspension was significantly correlated with the proportion of adhered MSCs immediately after the placement, but not 10 min later. Addition of FBS to the cryopreservation medium promoted a concentration-dependent increase in the proportion of microspike-positive cells.</p><p><strong>Conclusions: </strong>Thawed MSCs adhered better than cultured MSCs immediately after placement, but adhesion was similar for both MSC preparations after 10 min. Immediately after placement, the presence of microspikes was associated with better adhesion of synovial MSCs to the meniscus.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"53"},"PeriodicalIF":2.8,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9743635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10355986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1.","authors":"Hanye Liu,&nbsp;Guanghai Yan,&nbsp;Li Li,&nbsp;Dandan Wang,&nbsp;Yu Wang,&nbsp;Shan Jin,&nbsp;Zhehu Jin,&nbsp;Liangchang Li,&nbsp;Lianhua Zhu","doi":"10.1186/s12860-022-00451-4","DOIUrl":"https://doi.org/10.1186/s12860-022-00451-4","url":null,"abstract":"<p><strong>Background: </strong>Keloid is a benign proliferative fibrous disease featured by excessive fibroblast proliferation after skin injury. However, the mechanism of abnormal cell proliferation is still unclear. Herein, we investigated the mechanism of abnormal proliferation in keloids involving Sirtuin 1(SIRT1)/ Zeste Homolog 2 (EZH2)/ Runt-related transcription factor 3 (RUNX3).  METHODS: HE staining was used to observe the histopathological changes. Western blot was performed to detect SIRT1/EZH2/RUNX3 and cell cycle related proteins. RT-PCR detected EZH2 mRNA. After knockdown of EZH2 or overexpression of RUNX3, cell proliferation and cell cycle was analyzed. Immunoprecipitation was used to detect acetylated EZH2.</p><p><strong>Results: </strong>The results showed that overexpression of RUNX3 inhibited cell proliferation and arrested cell cycle at G1/S phase, whereas inhibition of SIRT1 promoted cell proliferation and G1/S phase of the cell cycle. Knockdown of EZH2 promoted the expression of RUNX3, inhibited cell proliferation and shortened the progression of G1 to S phase. Simultaneous knockdown of EZH2 and inhibition of SIRT1 reversed these effects. Inhibition of SIRT1 increased its protein stability by increasing EZH2 acetylation, thereby reducing the expression of RUNX3 and promoting cell proliferation.</p><p><strong>Conclusions: </strong>Conclusively, the SIRT1/EZH2/RUNX3 axis may be an important pathway in the regulation of abnormal proliferation in keloids.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"52"},"PeriodicalIF":2.8,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10693986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lncap-AI prostate cancer cell line establishment by Flutamide and androgen-free environment to promote cell adherent.","authors":"Huifeng Wang,&nbsp;Xihua Wei,&nbsp;Die Zhang,&nbsp;Weidong Li,&nbsp;Yanling Hu","doi":"10.1186/s12860-022-00453-2","DOIUrl":"https://doi.org/10.1186/s12860-022-00453-2","url":null,"abstract":"<p><strong>Background: </strong>To establish castration-resistant prostate cancer (CRPC) - Lncap androgen-independent (AI) cell line from Lncap androgen-dependent (AD) cell line, and explore the different molecular biological between these two cell lines.</p><p><strong>Methods: </strong>The Lncap-AD cell line was cultured and passaged 60 times over 16 months. The morphology of the Lncap-AI cell line was observed. AR levels identification were detected in qRT-PCR and Western Blot assay. CCK-8, EdU assay, wound healing assay and cell adhesion assays were used to observe the ability of proliferation, migration, and adhesion. SEM and TEM were used to observe microculture structure. At last, the PSA secrete ability was evaluated by Elisa assay.</p><p><strong>Results: </strong>The Lncap-AD cell line was cultured and passaged 60 times over 16 months. The Lncap-AI cell line showed a morphologic change at the end stage of culture, the cells turned slender and cell space turned separated compared to the Lncap-AD cell line. The relative levels of AR-related genes in the Lncap-AI cell line were up-regulation compared to the Lncap-AD cell line both in mRNA and protein levels. The expression of AR and HK2 proteins were influenced and down-regulation by Enzalutamide in the Lncap-AD cell line, but no obvious difference in Lncap-AI cell lines. Lncap-AI cell line showed strong viability of proliferation, migration, and adhesion by CCK-8, EdU assay, wound healing assay, and adhesion assay. The microstructure of Scanning Electron Microscopy (SEM) showed many synapses in the Lncap-AI cell line and PC3 cell line, but not in the Lncap-AD cell line. At last, the PSA secrete ability was evaluated by Elisa assay, and PCa cell lines showed no significant difference.</p><p><strong>Conclusion: </strong>Simulation of CRPC progression, Lncap-AD cell line turned to Lncap-AI cell line with androgen deprivation therapy.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"51"},"PeriodicalIF":2.8,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40709017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CARD9 contributes to ovarian cancer cell proliferation, cycle arrest, and cisplatin sensitivity.","authors":"Yanming Wang,&nbsp;Chao Wang,&nbsp;Yan Zhu","doi":"10.1186/s12860-022-00447-0","DOIUrl":"https://doi.org/10.1186/s12860-022-00447-0","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer recurrence and chemotherapy resistance are still urgent issues, and exploring the mechanisms of metastasis and chemotherapy resistance is beneficial to the development of therapeutic methods. Caspase recruitment domain family member 9 (CARD9) and homeobox B5 (HOXB5) are related and both are upregulated in ovarian cancer. This study aimed to define their functions in ovarian cancer cell proliferation, migration, and cisplatin sensitivity.</p><p><strong>Results: </strong>The levels of CARD9 were detected in acquired ovarian cancer tissues and cell lines. CARD9 was indeed abnormally upregulated in them. CARD9 knockdown significantly suppressed cell proliferation, colony formation, migration, cycle arrest, and cisplatin sensitivity. HOXB5 bound to the CARD9 promoter, and HOXB5 overexpression reversed the regulation by CARD9 knockdown in cells, as well as the activation of NF-κB signaling. This indicated that CARD9 was positively regulated by HOXB5 in ovarian cancer cells.</p><p><strong>Conclusion: </strong>Together, CARD9 is involved in ovarian cancer cell proliferation, migration, and cisplatin sensitivity via NF-κB signaling after transcriptional activation by HOXB5.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"49"},"PeriodicalIF":2.8,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10320729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the TGF-β/LIF signaling pathway mediated by SMADs during the cyst formation of Echinococcus in young children.","authors":"Shuang-Li Qin,&nbsp;Yun Guo,&nbsp;Shui-Xue Li,&nbsp;Ling Zhou,&nbsp;Azguli Maimaiti,&nbsp;Yusufu Akemu,&nbsp;Jun He,&nbsp;Hai-Xia Yao","doi":"10.1186/s12860-022-00452-3","DOIUrl":"https://doi.org/10.1186/s12860-022-00452-3","url":null,"abstract":"<p><strong>Objective: </strong>The present study aims to explore the correlation of the transforming growth factor β (TGF-β), drosophila mothers against decapentaplegic protein gene (SMAD) 2/3/4, and leukemia inhibitory factors (LIF) with the cyst formation of hepatic Echinococcus granulosus in young children.</p><p><strong>Methods: </strong>A total of 40 patients who met the diagnostic criteria for children's hydatid disease in people's Hospital of Xinjiang Uygur Autonomous Region between January 2020 and June 2021 were enrolled a s the study subjects. The cystic fluid of these children was collected as the case group and the corresponding infected viscera or pericystic tissue as the control group, with 40 cases in each group. In vitro cultured protoscolice of hydatid cyst, four groups including control group, LIF siRNA group, LIF factor group and SMAD4 siRNA group were divided by inhibiting TGF-β/SMADs signal pathway. Each assay was performed in triplicate. The expression of TGF-β, SMAD2/3/4 and LIF were detected.</p><p><strong>Results: </strong>The results of the clinical trial showed that the contents of SMAD2 and SMAD3 were increased in the case group compared with the control group; the differences were statistically significant (P < 0.05). The expression levels of TGF-β, Smad4, and LIF increased in the case group compared with the control group; however, the differences were not statistically significant. The results of further in vitro experiments, the expression levels of TGF-β, SMAD 2/3/4, and LIF after adding siRNA to interfere with Smad4 decreased in the case group compared with the control group; the differences were statistically significant (P < 0.05). Compared with the control group, the expression levels of TGF-β, SMAD2/3/4, and LIF increased after treatment with added LIF in the case group, and the expression levels of TGF-β, SMAD2/3/4, and LIF decreased after adding siRNA to interfere with LIF in the case group; the differences were all statistically significant (P < 0.05).</p><p><strong>Conclusion: </strong>SMAD2 and SMAD3 have a certain clinical relevance with hydatidosis in young children. The LIF expression level may be related to the cystic transformation of protoscoleces. It has been suggested that the TGF-β/Smads/LIF signaling pathway may be present in the process of protoscoleces cyst formation; this provides a research basis for the prevention and treatment of post-infection parasitism of E. multilocularis eggs in young children.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"50"},"PeriodicalIF":2.8,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40490141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosomal protein RPL5 regulates colon cancer cell proliferation and migration through MAPK/ERK signaling pathway.","authors":"Huahua Zhang,&nbsp;Junli Liu,&nbsp;Qingqing Dang,&nbsp;Xueru Wang,&nbsp;Jie Chen,&nbsp;Xiaoyin Lin,&nbsp;Na Yang,&nbsp;Juan Du,&nbsp;Haiyan Shi,&nbsp;Yong Liu,&nbsp;Jiming Han","doi":"10.1186/s12860-022-00448-z","DOIUrl":"https://doi.org/10.1186/s12860-022-00448-z","url":null,"abstract":"<p><strong>Background: </strong>Abnormal expression of ribosomal proteins has an important regulatory effect on the progression of cancer. RPL5 is involved in the progression of various malignancies, however, the role of RPL5 in colon cancer remains is still unclear.</p><p><strong>Methods: </strong>Data from TCGA and GTEx databases were used to analyze the RPL5 expression in pan-cancer. The expression level of RPL5 in clinical colon cancer tissue samples and human colon cancer cell lines was detected by western blotting; siRNA targeting RPL5 was designed, and its interference efficiency was verified by western blotting and RT-qPCR; CCK8 assay, clone formation assay, cell cycle assay, and cell scratch assay were used to observe the effect of RPL5 on colon cancer cell proliferation and migration; the changes of proteins related to MAPK/ERK signaling pathway were also detected using western blotting.</p><p><strong>Results: </strong>The expression level of RPL5 in colon cancer tissues and cell lines was significantly higher than that in adjacent tissues and NCM460 cells, respectively, and its expression level was higher in HCT116 cells and RKO cells. Knockdown of RPL5 significantly inhibited the proliferation and migration of HCT16 and RKO cells, and arrested the cell cycle in G0/G1 phase. Mechanistic studies revealed that the expression of p-MEK1/2, p-ERK, c-Myc were down-regulated, and the expression of FOXO3 was up-regulated after down-regulation of RPL5, ERK activator (TBHQ) could partially reverse the above-mentioned effects caused by siRPL5. Moreover, TBHQ could partially reverse the inhibitory effect of siRPL5 on the proliferation and migration of colon cancer cells. Collectively, RPL5 promoted colon cell proliferation and migration, at least in part, by activating the MAPK/ERK signaling pathway.</p><p><strong>Conclusion: </strong>RPL5 promoted colon cell proliferation and migration, at least in part, by activating the MAPK/ERK signaling pathway, which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"48"},"PeriodicalIF":2.8,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40688744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High levels of follicular fluid testosterone could impair oocyte developmental competency via affecting aryl hydrocarbon receptor pathway in PCOS patients.","authors":"Fatemeh Eini,&nbsp;Maryam Azizi Kutenaei,&nbsp;Tahereh Foroutan,&nbsp;Ensieh Salehi","doi":"10.1186/s12860-022-00449-y","DOIUrl":"https://doi.org/10.1186/s12860-022-00449-y","url":null,"abstract":"<p><strong>Background: </strong>Although hormonal and metabolic dysfunction have been recognized as a possible cause of polycystic ovarian syndrome (PCOS), the associations between hyperandrogenism and aryl hydrocarbon receptor (Ahr) signaling pathway remains controversial. The current study aimed to investigate the effect of hyperandrogenism on oocyte developmental competency via regarding Ahr signaling downstream pathway in granulosa cells.</p><p><strong>Materials and methods: </strong>Granulosa cells were collected from 45 PCOS patients under assisted reproductive technique (ART). Gene expression of Ahr downstream pathway was evaluated based on Reverse Transcription Q-PCR assay. Moreover the correlation was investigated between gene expression and hyperandrogenism, and oocyte developmental competency in PCOS.</p><p><strong>Results: </strong>From the 45 PCOS patients, 26 (64.44%) had a high level of follicular fluid testosterone (FFT). Based on the FFT level, two groups of PCOS: HFT (high level of FFT) and non-HFT, were shown significant differences in oocyte and embryo quality, and fertilization and cleavage rates. Moreover, the mean relative expressions of Ahr and Arnt genes were significantly higher in HFT -PCOS group (p < 0.01 and p < 0.01) respectively. Also, the significant positive correlations were obtained for Ahr, Arnt, Cyp1A1, and Cyp1B1 with incidence of clinical hyperandrogenism and FFT level. Besides, our results showed that Ahr, Cyp1A1, and Cyp1B1 gene expression was correlated significantly with fertilization rate.</p><p><strong>Conclusion: </strong>The present study suggested that hyperandrogenism could impair oocyte developmental competency via affecting Ahr signaling downstream pathway.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"47"},"PeriodicalIF":2.8,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9650820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40700130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of miR-451 in cholangiocarcinoma help the diagnsosi and promotes tumor progression.","authors":"Dengfang Guo,&nbsp;Qingling Wang,&nbsp;Jiancheng Huang,&nbsp;Zhanglin Hu,&nbsp;Chun Chen,&nbsp;Chun Zhang,&nbsp;Feng Lin","doi":"10.1186/s12860-022-00445-2","DOIUrl":"https://doi.org/10.1186/s12860-022-00445-2","url":null,"abstract":"<p><strong>Background: </strong>Cholangiocarcinoma is a kind of invasive malignant tumor followed by hepatocellular carcinoma. miR-451 was suggested to function as regulator in various human tumors, but its role in mediating tumor progression and predicting the prognosis of cholangiocarcinoma remains unknown. The clinical significance and biological function of miR-451 in cholangiocarcinoma were assessed in this study.</p><p><strong>Results: </strong>The tissue and serum expression of miR-451 was decreased in cholangiocarcinoma compared with corresponding normal samples. The downregulation of miR-451 was associated with the progressive TNM stage and positive lymph node metastasis of patients. miR-451 was identified to be an indicator of the diagnosis and prognosis of cholangiocarcinoma distinguishing cholangiocarcinoma patients from healthy volunteers and predicting the poor outcome of patients. miR-451 also served as a tumor suppressor negatively regulating the cellular processes of cholangiocarcinoma.</p><p><strong>Conclusions: </strong>miR-451 played a vital role in the early detection and risk prediction of cholangiocarcinoma. miR-451 also suppressed the progression of cholangiocarcinoma, which provides a potential therapeutical target for cholangiocarcinoma treatment.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"46"},"PeriodicalIF":2.8,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40453694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetaminophen changes the RNA m⁶A levels and m⁶A-related proteins expression in IL-1β-treated chondrocyte cells.","authors":"Jie Gao,&nbsp;Yan Li,&nbsp;Zijin Liu,&nbsp;Dong Wang,&nbsp;Huawu Zhang","doi":"10.1186/s12860-022-00444-3","DOIUrl":"https://doi.org/10.1186/s12860-022-00444-3","url":null,"abstract":"<p><strong>Background: </strong>Acetaminophen is commonly recommended for the early analgesia of osteoarthritis. However, the molecular mechanism by which it acts remains unknown. The aim of this study is to investigate the effect of acetaminophen on inflammation and extracellular matrix degradation in human chondrocytes, and the possible molecular mechanisms involved in its effect.</p><p><strong>Methods: </strong>The normal chondrocyte cell line C28/I2 was treated with interleukin-1β to mimic the inflammatory state. Acetaminophen and the methylation inhibitor (cycloleucine) were used to treat interleukin-1β-induced C28/I2 cells. The expression of RNA N⁶-methyladenosine -related proteins was detected by RT-qPCR and western blot. The total RNA N⁶-methyladenosine level was measured by dot blot analysis and enzyme linked immunosorbent assay. The levels of interleukin-6, interleukin-8 and anti-tumor necrosis factor-α were measured by enzyme linked immunosorbent assay. The extracellular matrix synthesis and degradation were examined by western blot.</p><p><strong>Results: </strong>After interleukin-1β stimulated C28/I2 cells, the intracellular RNA N⁶-methyladenosine level increased, and the expression of regulatory proteins also changed, mainly including the increased expression of methyltransferase like 3 and the downregulated expression of AlkB family member 5. The use of cycloleucine inhibited interleukin-1β-induced inflammation and extracellular matrix degradation by inhibiting RNA N⁶-methyladenosine modification. In contrast, acetaminophen treatment counteracted interleukin-1β-induced changes in RNA N⁶-methyladenosine levels and regulatory protein expression. Furthermore, acetaminophen treatment of interleukin-1β-induced C28/I2 cells inhibited the secretion of interleukin-6, interleukin-8 and anti-tumor necrosis factor-α, down-regulated the expression of matrix metalloproteinase-13 and Collagen X, and up-regulated the expression of collagen II and aggrecan. In addition, AlkB family member 5 overexpression activated interleukin-1β-induced chondrocyte viability and suppressed inflammation and extracellular matrix degradation.</p><p><strong>Conclusion: </strong>Acetaminophen affects inflammatory factors secretion and extracellular matrix synthesis of human chondrocytes by regulating RNA N⁶-methyladenosine level and N⁶-methyladenosine-related protein expression. Stimulation of the normal chondrocyte cell line C28/I2 with the cytokine IL-1β (10 μM) mimics the inflammatory state in vitro. Acetaminophen (Ace, 50 μg/mL) changes the m⁶A related proteins expression and the total RNA m⁶A levels in IL-1β-treated chondrocyte cells. Furthermore, regulation of RNA m⁶A levels (by methylation inhibitor Cyc and/or Ace) affects IL-1β-induced inflammatory cytokines secretion and extracellular matrix synthesis in C28/I2 cells.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"45"},"PeriodicalIF":2.8,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}