Journal of Molecular Histology最新文献

{"title":"Differential tempol effects in prostatic cancer: angiogenesis and short- and long-term treatments","authors":"Felipe Rabelo Santos, Isabela Maria Urra Rossetto, Fabio Montico, Celina de Almeida Lamas, Valéria Helena Alves Cagnon","doi":"10.1007/s10735-024-10187-4","DOIUrl":"https://doi.org/10.1007/s10735-024-10187-4","url":null,"abstract":"<p>Prostate cancer (PCa) is the second cause of cancer death among men worldwide. Several processes are involved in the development and progression of PCa such as angiogenesis, inflammation and oxidative stress. The present study investigated the effect of short- or long-term Tempol treatment at different stages of prostate adenocarcinoma progression, focusing on angiogenic, proliferative, and stromal remodeling processes in TRAMP mice. The dorsolateral lobe of the prostate of TRAMP mice were evaluated at two different stages of PCa progression; early and late stages. Early stage was again divided into, short- or long-term. 50 mg/kg Tempol dose was administered orally. The results demonstrated that Tempol mitigated the prostate histopathological lesion progressions in the TRAMP mice in all treated groups. However, Tempol increased molecules involved in the angiogenic process such as CD31 and VEGFR2 relative frequencies, particularly in long-term treatment. In addition, Tempol upregulated molecule levels involved in angiogenesis and stromal remodeling process VEGF, TGF-β1, VE-cadherin and vimentin, particularly, in T8-16 group. Thus, it was concluded that Tempol treatment delayed prostatic lesion progression in the dorsolateral lobe of the TRAMP mice. However, Tempol also led to pro-angiogenic effects and glandular stromal microenvironment imbalance, especially, in the long-term treatment.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140324714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis","authors":"Peiwei Cong, Bing Shang, Lina Zhang, Zhaoli Wu, Yanan Wang, Jia Li, Lin Zhang","doi":"10.1007/s10735-024-10183-8","DOIUrl":"https://doi.org/10.1007/s10735-024-10183-8","url":null,"abstract":"<p>Polycystic ovary syndrome (PCOS) is an endocrine disease, and its pathogenesis and treatment are still unclear. Hexokinase domain component 1 (HKDC1) participates in regulating mitochondrial function and glycolysis. However, its role in PCOS development remains unrevealed. Here, female C57BL/6 mice were intraperitoneally injected with dehydroepiandrosterone (DHEA; 60 mg/kg body weight) to establish an in vivo model of PCOS. In vitro, KGN cells, a human ovarian granular cell line, were used to explore the potential mechanisms. DHEA-treated mice exhibited a disrupted estrus cycle, abnormal hormone levels, and insulin resistance. Dysfunction in mitochondria and glycolysis is the main reason for PCOS-related growth inhibition of ovarian granular cells. Here, we found that the structure of mitochondria was impaired, less ATP was generated and more mitochondrial Reactive Oxygen Species were produced in HKDC1-silenced KGN cells. Moreover, HKDC1 knockdown inhibited glucose consumption and decreased the production of glucose-6-phosphate and lactic acid. Conclusively, HKDC1 protects ovarian granulocyte cells from DHEA-related damage at least partly by preserving mitochondrial function and maintaining glycolysis.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140116393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of miR-26b and miR-27b expressions and the effect of quercetin on fibrosis in experimental pulmonary fibrosis.","authors":"Çağrı Toker, Yurdun Kuyucu, Dilek Şaker, Samet Kara, Bilge Güzelel, Ufuk Özgü Mete","doi":"10.1007/s10735-023-10168-z","DOIUrl":"10.1007/s10735-023-10168-z","url":null,"abstract":"<p><p>In this study, investigation of the effects of Quercetin on Bleomycin-induced pulmonary fibrosis and fibrosis-associated molecules miR-26b and miR-27b was aimed. Control group was given 10% saline on the 0th day, and saline was administered for 21 days starting from the 8th day. Group 2 was given 50 mg/kg Quercetin for 21 days starting from the 8th day. Group 3 was given 10 mg/kg Bleomycin Sulfate on day 0, and sacrificed on the 22nd and 29th day. Group 4 was given 10 mg/kg Bleomycin Sulfate on the 0th day, and was given 50 mg/kg Quercetin for 14 days, and 21 days starting from day 8. Lung tissues were examined using light and electron microscopic, immunohistochemical and molecular biological methods. Injury groups revealed impaired alveolar structure, collagen accumulation and increased inflammatory cells in interalveolar septum. Fibrotic response was decreased and the alveolar structure was improved with Quercetin treatment. α-SMA expressions were higher in the injury groups, but lower in the treatment groups compared to the injury groups. E-cadherin expressions were decreased in the injury groups and showed stronger immunoreactivity in the treatment groups compared to the injury groups. miR-26b and miR-27b expressions were lower in the injury groups than the control groups, and higher in the treatment groups than the injury groups. Quercetin can be considered as a new treatment agent in the idiopathic pulmonary fibrosis, since it increases the expression levels of miR-26b and miR-27b which decrease in fibrosis, and has therapeutic effects on the histopathological changes.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49672970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteopontin: an essential regulatory protein in idiopathic pulmonary fibrosis.","authors":"Xiaoyu Zhu, Jie Ji, Xiaodong Han","doi":"10.1007/s10735-023-10169-y","DOIUrl":"10.1007/s10735-023-10169-y","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic lung disease characterized by abnormal proliferation and activation of fibroblasts, excessive accumulation of extracellular matrix (ECM), inflammatory damage, and disrupted alveolar structure. Despite its increasing morbidity and mortality rates, effective clinical treatments for IPF remain elusive. Osteopontin (OPN), a multifunctional ECM protein found in various tissues, has been implicated in numerous biological processes such as bone remodeling, innate immunity, acute and chronic inflammation, and cancer. Recent studies have highlighted the pivotal role of OPN in the pathogenesis of IPF. This review aims to delve into the involvement of OPN in the inflammatory response, ECM deposition, and epithelial-mesenchymal transition (EMT) during IPF, and intends to lay a solid theoretical groundwork for the development of therapeutic strategies for IPF.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50156781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orientin alleviates ox-LDL-induced oxidative stress, inflammation and apoptosis in human vascular endothelial cells by regulating Sestrin 1 (SESN1)-mediated autophagy","authors":"Feng Gao, Yongcheng Zhao, Bin Zhang, Chunwei Xiao, Zhanfa Sun, Yuan Gao, Xueyong Dou","doi":"10.1007/s10735-023-10176-z","DOIUrl":"https://doi.org/10.1007/s10735-023-10176-z","url":null,"abstract":"<p>Endothelial cells are a crucial component of the vessel-tissue wall and exert an important role in atherosclerosis (AS). To explore the role of Orientin in AS, human vascular endothelial cells (HUVECs) were induced by oxidized low-density lipoprotein (ox-LDL) to simulate the vascular endothelial injury during AS. Cell viability was detected by CCK-8 assay. Oxidative stress and inflammation related markers were measured using kits, RT-qPCR or western blot. Besides, cell apoptosis was assessed with TUNEL staining and cell autophagy was evaluated by LC3 immunofluorescent staining. Additionally, western blot was utilized to evaluate the expression of Sestrin 1 (SESN1) and proteins in AMPK/mTOR signaling. Afterwards, SESN1 was silenced to determine the expression of autophagy-related proteins. The further application of autophagy inhibitor 3-methyladenine (3-MA) was used to clarify the regulatory mechanism of Orientin on autophagy. Results showed that the decreased viability of HUVECs caused by ox-LDL induction was elevated by Orientin. Oxidative stress and inflammation were also attenuated after Orientin addition in HUVECs under ox-LDL condition. Moreover, Orientin suppressed apoptosis and induced autophagy of HUVECs stimulated by ox-LDL, accompanied by enhanced level of phospho (p)-AMPK and declined level of p-mTOR. Interestingly, SESN1 level was elevated by Orientin, and SESN1 depletion alleviated autophagy and reduced p-AMPK expression but enhanced p-mTOR expression. The further experiments indicated that SESN1 silencing or 3-MA addition reversed the inhibitory effects of Orientin on the oxidative stress, inflammation and apoptosis of HUVECs. Collectively, Orientin could induce autophagy by activating SESN1 expression, thereby regulating AMPK/mTOR signaling in ox-LDL-induced HUVECs.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139079169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VNS improves VSMC metabolism and arteriogenesis in infarcted hearts through m/n-AChR-Akt-SDF-1α in adult male rats","authors":"","doi":"10.1007/s10735-023-10171-4","DOIUrl":"https://doi.org/10.1007/s10735-023-10171-4","url":null,"abstract":"<h3>Abstract</h3> <p>Vagal nerve stimulation (VNS) provides a novel therapeutic strategy for injured hearts by activating cholinergic anti-inflammatory pathways. However, little information is available on the metabolic pattern and arteriogenesis of VSMCs after MI. VNS has been shown to stimulate the expression of CPT1α, CPT1β, Glut1, Glut4 and SDF-1α in coronary VSMCs, decreasing the number of CD68-positive macrophages while increasing CD206-positive macrophages in the infarcted hearts, leading to a decrease in TNF-α and IL-1β accompanied by a reduced ratio of CD68- and CD206-positive cells, which were dramatically abolished by atropine and mecamylamine in vivo. Knockdown of SDF-1α substantially abrogated the effect of VNS on macrophagecell alteration and inflammatory factors in infarcted hearts. Mechanistically, ACh induced SDF-1α expression in VSMCs in a dose-dependent manner. Conversely, atropine, mecamylamine, and a PI3K/Akt inhibitor completely eliminated the effect of ACh on SDF-1α expression. Functionally, VNS promoted arteriogenesis and improved left ventricular performance, which could be abolished by Ad-shSDF-1α. Thus, VNS altered the VSMC metabolism pattern and arteriogenesis to repair the infarcted heart by inducing SDF-1α expression, which was associated with the m/nAChR-Akt signaling pathway.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139079172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOB1 and TOB2 mark distinct RNA processing granules in differentiating lens fiber cells","authors":"Rafaela C. Perez, Xenia Yang, Mary Familari, Gemma Martinez, Frank J. Lovicu, Gary R Hime, Robb U de Iongh","doi":"10.1007/s10735-023-10177-y","DOIUrl":"https://doi.org/10.1007/s10735-023-10177-y","url":null,"abstract":"<p>Differentiation of lens fiber cells involves a complex interplay of signals from growth factors together with tightly regulated gene expression via transcriptional and post-transcriptional regulators. Various studies have demonstrated that RNA-binding proteins, functioning in ribonucleoprotein granules, have important roles in regulating post-transcriptional expression during lens development. In this study, we examined the expression and localization of two members of the BTG/TOB family of RNA-binding proteins, TOB1 and TOB2, in the developing lens and examined the phenotype of mice that lack <i>Tob1</i>. By RT-PCR, both <i>Tob1</i> and <i>Tob2</i> mRNA were detected in epithelial and fiber cells of embryonic and postnatal murine lenses. In situ hybridization showed <i>Tob1</i> and <i>Tob2</i> mRNA were most intensely expressed in the early differentiating fibers, with weaker expression in anterior epithelial cells, and both appeared to be downregulated in the germinative zone of E15.5 lenses. TOB1 protein was detected from E11.5 to E16.5 and was predominantly detected in large cytoplasmic puncta in early differentiating fiber cells, often co-localizing with the P-body marker, DCP2. Occasional nuclear puncta were also observed. By contrast, TOB2 was detected in a series of interconnected peri-nuclear granules, in later differentiating fiber cells of the inner cortex. TOB2 did not appear to co-localize with DCP2 but did partially co-localize with an early stress granule marker (EIF3B). These data suggest that TOB1 and TOB2 are involved with different aspects of the mRNA processing cycle in lens fiber cells. In vitro experiments using rat lens epithelial explants treated with or without a fiber differentiating dose of FGF2 showed that both TOB1 and TOB2 were up-regulated during FGF-induced differentiation. In differentiating explants, TOB1 also co-localized with DCP2 in large cytoplasmic granules. Analyses of <i>Tob1</i>^<i>-/-</i> mice revealed relatively normal lens morphology but a subtle defect in cell cycle arrest of some cells at the equator and in the lens fiber mass of E13.5 embryos. Overall, these findings suggest that TOB proteins play distinct regulatory roles in RNA processing during lens fiber differentiation.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic lncRNA FAM215A promotes the malignant cell phenotypes of acute myeloid leukemia (AML) cell lines","authors":"Lin Li, Liuyan Xin, Xiang Yang, Zhengrong Zou","doi":"10.1007/s10735-023-10174-1","DOIUrl":"https://doi.org/10.1007/s10735-023-10174-1","url":null,"abstract":"<p>Acute myeloid leukemia (AML) is a form of blood cancer that arise as a result of clonal proliferation of malignant myeloid precursors acquiring genetic abnormalities. Primary resistance to initial treatment and disease recurrence continues to be huge challenge in treating AML. Herein, GSE114868 was analyzed for differentially-expressed lncRNAs between AML patients’ mononucleated cells and healthy normal control mononucleated cells and 191 lncRNAs were significantly deregulated in AML patients’ mononucleated cells. The correlation between candidate lncRNAs and AML patients’ overall survival was analyzed and 6 lncRNAs, including MIR181A1HG, TRAF3IP2-AS1, STARD4-AS1, E2F3-IT1, FAM215A, and HHIP-AS1 were dramatically linked to AML patients’ OS. Using a Cox proportional-hazards model, we identified risk factors and found FAM215A as a risk factor for AML patients’ prognosis. The expression level of FAM215A showed to be upregulated within blood samples and cells. Genes correlated with FAM215A were correlated to cell division, modulation of cell apoptosis, and modulation of programmed cell death. FAM215A knockdown inhibited AML cell viability, elicited G0/G1-phase arrest of cell cycle, enhanced cell apoptosis, increased proapoptotic Bax and cleaved-caspase3 levels, and decreased antiapoptotic Bcl2. FAM215A overexpression exerted opposite effects on AML cells. Conclusively, FAM215A serves as an oncogenic lncRNA in AML, promoting cell viability, relieving cell cycle arrest, and suppressing cell apoptosis. FAM215A might be un underlying biological prognostic marker and therapeutic target for AML.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139079906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silenced-C5ar1 improved multiple organ injury in sepsis rats via inhibiting neutrophil extracellular trap","authors":"Bin Shen, Qikai Shen, Qingqiu Zeng, Lingyan Zhang, Xiaofeng Li","doi":"10.1007/s10735-023-10172-3","DOIUrl":"https://doi.org/10.1007/s10735-023-10172-3","url":null,"abstract":"<p>Sepsis has a systemic inflammatory response syndrome caused by infection. While neutrophils play contradictory roles in different stages of sepsis. Neutrophils have been proven to play an antibacterial role by producing neutrophil extracellular traps (NETs). Although the NET is beneficial to bacteria resistance, abnormal NET increases tissue damage. The complement C5a receptor 1 (C5ar1) is a gene related to strong inflammatory reactions and is found to be associated with inflammatory factors. This study found that there were 45 down-regulated genes and 704 up-regulated genes in sepsis rats by transcriptome sequencing. And those genes were significantly related to inflammation and immunity by GO and KEGG enrichment analysis involving the chemokine signaling pathway, the Toll-like receptor (TLR) signaling pathway, and the Fc gamma R-mediated phagocytosis. Additionally, the C5ar1 gene was significantly upregulated with interesting potential in sepsis and used for further study. This study used cecum ligation and puncture (CLP) rats that were respectively injected intravenously with PBS or the lentivirus vector to explore the effect of C5ar1 on CLP rats. It demonstrated that silenced- C5ar1 inhibited the ALT, AST, BUN, and CREA levels, improved the lung and spleen injury, and reduced the TNF-α, IL-6, IL-1β, IL-10, cf-DNA, and cfDNA/MPO levels. Additionally, silenced C5ar1 inhibited the TLR2, TLR4, and peptidylarginine deiminase 4 expression levels, which suggested the improvement of silenced C5ar1 on sepsis via inhibiting NETs and the TLR signaling pathway. This study provides a basis and new direction for the study of treatment on sepsis.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The lncRNA lnc-TSI antagonizes sorafenib resistance in hepatocellular carcinoma via downregulating miR-4726-5p expression and upregulating KCNMA1 expression","authors":"Fengrong Chen, Jiong Jiang, Dong Liu, Hong Li, Lei Dong, Yahua Song, Ying Zhang, Jing Wang, Yun Qin, Gang Zhao","doi":"10.1007/s10735-023-10173-2","DOIUrl":"https://doi.org/10.1007/s10735-023-10173-2","url":null,"abstract":"<p>Acquired drug resistance is a main reason for limiting the application of sorafenib in HCC treatment. This study aimed to explore the role and mechanisms of a novel long non-coding RNA (lncRNA), lnc-TSI, in sorafenib resistance of HCC. The interaction between lnc-TSI and miR-4726-5p, and miR-4726-5p and KCNMA1 were predicted using bioinformatic tools. Expression of the molecules in the lnc-TSI/miR-4726-5p/KCNMA1 axis in clinical samples and cell lines, as well as the sorafenib resistant HCC cell lines, was determined using qRT-PCR or western blotting. Expressions of lnc-TSI, miR-4726-5p, and KCNMA1 were manipulated in HepG2 and Huh7 cells through plasmid transfection or lentivirus infection. The CCK-8, flow cytometry, and Tunel assays were employed to determine the role of this axis on sorafenib resistance of HCC. A xenograft model was established using sorafenib-resistant HepG2 and Huh7 cells followed by in vivo sorafenib treatments to confirm the in vitro findings. Lnc-TSI and KCNMA1 expressions were significantly downregulated in HCC clinical samples and cell lines, especially in sorafenib resistance ones, while mi-4726-5p presented a reversed expression pattern. Lnc-TSI interacted with miR-4726-5p, and Lnc-TSI acts as a ceRNA via sponging miR-4726-5p in HCC cells. Overexpression of lnc-TSI and KCNMA1 promoted apoptosis and decreased cell viability of sorafenib-treated HCC cells, thus alleviated sorafenib resistance. miR-4726-5p mimic reversed the KCNMA1-mediated sorafenib sensitivity-promoting effect, while additional overexpression of lnc-TSI reversed the effect of miR-4726-5p. In vivo analysis also showed that overexpression of ln-TSI diminished sorafenib resistance in mice inoculated with sorafenib-resistant HCC cells via increasing KCNMA1 expression and decreasing miR-4726-5p expression. The lnc-TSI/miR-4726-5p/KCNMA1 axis plays a critical role in regulating the resistance of HCC to sorafenib, and might serve as a therapeutic target to manage sorafenib resistance of HCC in clinic.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139079134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}