Yuanxing Han, Nueryemu Maimaiti, Yue Sun, Juan Yao
{"title":"Knockout of KDM3A in MDA-MB-231 breast cancer cells inhibits tumor malignancy and promotes apoptosis","authors":"Yuanxing Han, Nueryemu Maimaiti, Yue Sun, Juan Yao","doi":"10.1007/s10735-023-10178-x","DOIUrl":"https://doi.org/10.1007/s10735-023-10178-x","url":null,"abstract":"<p>The histone lysine demethylase 3 A (KDM3A) is vital for the regulation of cancer physiology and pathophysiology. The purpose of this study was to investigate the effect of KDM3A expression with triple-negative breast cancer (TNBC) invasion and metastasis. In our results, knockout of KDM3A in TNBC MDA-MB-231 cells promoted apoptosis and inhibited the proliferation, invasion and metastasis of MDA-MB-231 cells. In addition, we found that in vivo experiments indicated that the growth, invasion and metastasis of metastatic neoplasms were significantly inhibited by knockout of KDM3A in a TNBC metastasis model. These findings suggest that KDM3A may be a potential therapeutic target for the treatment and prevention of TNBC, providing a critical theoretical basis for the effective prevention or treatment of breast cancer disease.</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":"139079230","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}
Xiaoting Xi, Qianbo Chen, Jia Ma, Xuewei Wang, Junyan Zhang, Yan Li
{"title":"Sestrin2 ameliorates diabetic retinopathy by regulating autophagy and ferroptosis","authors":"Xiaoting Xi, Qianbo Chen, Jia Ma, Xuewei Wang, Junyan Zhang, Yan Li","doi":"10.1007/s10735-023-10180-3","DOIUrl":"https://doi.org/10.1007/s10735-023-10180-3","url":null,"abstract":"<p>Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. The aim of this study was to explore the effect of Sestrin2 on DR through the regulation of autophagy and ferroptosis levels and its mechanism. In vitro and in vivo DR models were established by high glucose (HG) and streptozotocin (STZ) induction of ARPE-19 human retinal pigment epithelial cells and C57BL/6 mice, respectively. In this study, we demonstrated that after HG treatment, the activity of ARPE-19 cells was decreased, the apoptosis rate was increased, endoplasmic reticulum (ER) stress was activated, autophagy levels were decreased, and ferroptosis levels were increased. Overexpression of Sestrin2 enhanced cell viability, reduced apoptosis and ferroptosis, and enhanced autophagy. However, the effect of overexpression of Sestrin2 was attenuated after the addition of the STAT3 phosphorylation activator Colivelin TFA (C-TFA), the mTOR pathway activator MHY1485 or the autophagy inhibitor 3-methyladenine (3-MA). In addition, the effect of Sestrin2 knockdown on cells was opposite to the effect of overexpression of Sestrin2, while the effect of Sestrin2 knockdown was attenuated after treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Animal experiments also confirmed the results of cell experiments and attenuated the effects of overexpression of Sestrin2 after injection of the ferroptosis activators erastin or 3-MA. Our study revealed that Sestrin2 inhibits ferroptosis by inhibiting STAT3 phosphorylation and ER stress and promoting autophagy levels, thereby alleviating DR.</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":"139079292","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}
Yao Wang, Hongfei Tong, Juxiang Wang, Linglong Hu, Zhen Huang
{"title":"LRRC1 knockdown downregulates MACF1 to inhibit the malignant progression of acute myeloid leukemia by inactivating β-catenin/c-Myc signaling","authors":"Yao Wang, Hongfei Tong, Juxiang Wang, Linglong Hu, Zhen Huang","doi":"10.1007/s10735-023-10170-5","DOIUrl":"https://doi.org/10.1007/s10735-023-10170-5","url":null,"abstract":"<p>Acute myeloid leukemia (AML) is a hematologic disease associated with genetic abnormalities. This study aimed to explore the role of leucine-rich repeat-containing protein 1 (LRRC1) in the malignant activities of AML and to reveal the molecular mechanism related to microtubule actin cross-linking factor 1 (MACF1). GEPIA database was used to analyze the expression of LRRC1 in bone marrow tissues of AML patients and the correlation between LRRC1 expression and survival analysis. LRRC1 was knocked down to assess the change of AML cell proliferation, cell cycle and apoptosis using CCK-8 assay and flow cytometry. Besides, the contents of extracellular acidification and oxygen consumption rates were measured to evaluate the glycolysis. Additionally, the interaction between LRRC1 and MACF1 predicted by MEM database and was verified by co-immunoprecipitation (Co-IP) assay. Then, MACF1 was overexpressed to conduct the rescue experiments. Expression of proteins in β-catenin/c-Myc signaling was detected by western blot. Finally, AML xenograft mouse model was established to observe the impacts of LRRC1 silencing on the tumor development. Notably upregulated LRRC1 expression was observed in bone marrow tissues of AML patients and AML cells, and patients with the higher LRRC1 expression displayed the lower overall survival. LRRC1 depletion promoted cell cycle arrest and apoptosis and inhibited the glycolysis. Co-IP confirmed the interaction between LRRC1 and MACF1. MACF1 upregulation relieved the impacts of LRRC1 knockdown on the malignant activities of AML cells. Moreover, LRRC1 silencing inhibited the development of xenograft tumor growth of HL-60 cells in nude mice, suppressed MACF1 expression and inactivated the β-catenin/c-Myc signaling. Collectively, LRRC1 knockdown suppressed proliferation, glycolysis and promoted apoptosis in AML cells by downregulating MACF1 expression to inactivate β-catenin/c-Myc signaling.</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":"139079128","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}
Tannaz Taraz, Mohadeseh Mahmoudi-Ghehsareh, Nastaran Asri, Ehsan Nazemalhosseini-Mojarad, Mostafa Rezaei-Tavirani, Somayeh Jahani-Sherafat, Ali Naseh, Mohammad Rostami-Nejad
{"title":"Overview of the compromised mucosal integrity in celiac disease","authors":"Tannaz Taraz, Mohadeseh Mahmoudi-Ghehsareh, Nastaran Asri, Ehsan Nazemalhosseini-Mojarad, Mostafa Rezaei-Tavirani, Somayeh Jahani-Sherafat, Ali Naseh, Mohammad Rostami-Nejad","doi":"10.1007/s10735-023-10175-0","DOIUrl":"https://doi.org/10.1007/s10735-023-10175-0","url":null,"abstract":"<p>Intestinal epithelium is a dynamic cellular layer that lines the small-bowel and makes a relatively impenetrable barrier to macromolecules. Intestinal epithelial cell polarity is crucial in coordinating signalling pathways within cells and mainly regulated by three conserved polarity protein complexes, the Crumbs (Crb) complex, partitioning defective (PAR) complex, and Scribble (Scrib) complex. Polarity proteins regulate the proper establishment of the intercellular junctional complexes including tight junctions (TJs), adherence junctions (AJs), and desmosomes which hold epithelial cells together and play a major role in maintaining intestinal barrier integrity. Impaired intestinal epithelial cell polarity and barrier integrity result in irreversible immune responses, the host- microbial imbalance and intestinal inflammatory disorders. Disassembling the epithelial tight junction and augmented paracellular permeability is a conspicuous hallmark of celiac disease (CD) pathogenesis. There are several dietary components that can improve intestinal integrity and function. The aim of this review article is to summarize current information about the association of polarity proteins and AJC damages with pathogenesis of CD.</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":"139080016","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}
Bangsheng Chen, Lian Tan, Ying Wang, Lei Yang, Jiequan Liu, Danqi Chen, Shuaishuai Huang, Feiyan Mao, Jiangfang Lian
{"title":"LOC102549726/miR-760-3p network is involved in the progression of ISO-induced pathological cardiomyocyte hypertrophy via endoplasmic reticulum stress","authors":"Bangsheng Chen, Lian Tan, Ying Wang, Lei Yang, Jiequan Liu, Danqi Chen, Shuaishuai Huang, Feiyan Mao, Jiangfang Lian","doi":"10.1007/s10735-023-10166-1","DOIUrl":"10.1007/s10735-023-10166-1","url":null,"abstract":"<div><p>Pathological cardiac hypertrophy (CH) is featured by myocyte enlargement and cardiac malfunction. Multiple signaling pathways have been implicated in diverse pathological and physiological processes in CH. However, the function of LOC102549726/miR-760-3p network in CH remains unclear. Here, we characterize the functional role of LOC102549726/miR-760-3p network in CH and delineate the underlying mechanism. The expression of LncRNA LOC102549726 and hypertrophic markers was significantly increased compared to the control, while the level of miR-760-3p was decreased. Next, we examined ER stress response in a hypertrophic cardiomyocyte model. The expression of ER stress markers was greatly enhanced after incubation with ISO. The hypertrophic reaction, ER stress response, and increased potassium and calcium ion channels were alleviated by genetic downregulation of LOC102549726. It has been demonstrated that LOC102549726 functions as a competitive endogenous RNA (ceRNA) of miR-760-3p. Overexpression of miR-760-3p decreased cell surface area and substantially mitigated ER stress response; protein levels of potassium and calcium channels were also significantly up-regulated compared to the NC control. In contrast, miR-760-3p inhibition increased cell size, aggravated CH and ER stress responses, and reduced ion channels. Collectively, in this study we demonstrated that the LOC102549726/miR-760-3p network was a crucial regulator of CH development. Ion channels mediate the ER stress response and may be a downstream sensor of the LOC102549726/miR-760-3p network. Therefore, these findings advance our understanding of pathological CH and provide new insights into therapeutic targets for cardiac remodeling.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondria as a target for exercise-mitigated type 2 diabetes","authors":"Jingjing Tian, Jingcheng Fan, Tan Zhang","doi":"10.1007/s10735-023-10158-1","DOIUrl":"10.1007/s10735-023-10158-1","url":null,"abstract":"<div><p>Type 2 diabetes mellitus (T2DM) is one of most common metabolic diseases and continues to be a leading cause of death worldwide. Although great efforts have been made to elucidate the pathogenesis of diabetes, the underlying mechanism still remains unclear. Notably, overwhelming evidence has demonstrated that mitochondria are tightly correlated with the development of T2DM, and the defects of mitochondrial function in peripheral insulin-responsive tissues, such as skeletal muscle, liver and adipose tissue, are crucial drivers of T2DM. Furthermore, exercise training is considered as an effective stimulus for improving insulin sensitivity and hence is regarded as the best strategy to prevent and treat T2DM. Although the precise mechanisms by which exercise alleviates T2DM are not fully understood, mitochondria may be critical for the beneficial effects of exercise.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688268","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}
Bin Jiang, Mingming Tang, Si Shi, Haijing Xie, Si Pan, Lin Zhang, Juping Sheng
{"title":"Effects of abnormal expression of CD73 on malignant phenotype of nasopharyngeal carcinoma","authors":"Bin Jiang, Mingming Tang, Si Shi, Haijing Xie, Si Pan, Lin Zhang, Juping Sheng","doi":"10.1007/s10735-023-10165-2","DOIUrl":"10.1007/s10735-023-10165-2","url":null,"abstract":"<div><p>Cluster of differentiation (CD) 73, encoded by the <i>NT5E</i> gene, plays important enzymatic and non-enzymatic roles in cells. There is growing evidence show that CD73 is a key regulator in the development of tumor. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in east and southeast Asia. It is urgent to know more about the mechanism of NPC development and find diagnostic markers for the patients. In this research, we carried out western blot, immunohistochemistry and qRT-PCR to investigate the expression level of CD73 and found that NPC tissues had higher level of CD73 than normal tissues. We also detected the relationship between its expression level with the clinicopathological features and prognosis of NPC patients. The results showed that CD73 expression was related to the clinical stages, lymph node metastasis and survival state of NPC patients. More importantly, patients with higher expression of CD73 had poorer prognosis. Then, CD73 was knocked down in NPC cells (CNE2 and CNE1), and its effects on cell proliferation and migration were investigated by CCK8, colony formation, Transwell and wound-healing assays. We found that knocking down the expression of CD73 in NPC cells could inhibit cells malignant phenotype. Collectively, CD73 plays important roles in NPC malignant behavior and might act as a novel target for the diagnosis and treatment of NPC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-023-10165-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 circSNX14 functions as a tumor suppressor via the miR-562/ LATS2 pathway in hepatocellular carcinoma cells","authors":"Yan Wu, Yaowei Yang, Xin Yi, Liwen Song","doi":"10.1007/s10735-023-10157-2","DOIUrl":"10.1007/s10735-023-10157-2","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) play critical roles in the initiation and progression of various cancers. However, the potential functional roles of circSNX14 in hepatocellular carcinoma (HCC) remain largely unknown. CircSNX14 expression pattern was analyzed in HCC tissues and cell lines via qRT-PCR. The effects of circSNX14 on cell proliferation, invasion, angiogenesis, and Epithelial-mesenchymal transition (EMT) were investigated by overexpression experiments. The role of circSNX14 in the tumorigenesis of HCC cells was examined using in vivo xenograft mouse model. The interaction between circSNX14, miR-562, and Large Tumor Suppressor Kinase 2 (LATS2) mRNA was confirmed by Luciferase reporter assay and RNA immunoprecipitation (RIP) analysis. CircSNX14 was significantly down-regulated in HCC tissues and cell lines, and its down-regulation was correlated with a poor prognosis in HCC patients. In the following functional experiments, circSNX14 overexpression remarkably suppressed the proliferation and invasion of HCC cells, and attenuated the mesenchymall status. circSNX14 overexpression also suppressed the tumorigenesis of HCC cells in the mouse model. We further revealed the interaction of circSNX14 and miR-562, and miR-562 could suppress the expression of LATS2 by interacting with its mRNA. The negative correlation of circSNX14 and miR-562, negative correlation of miR-562 and LATS2, and positive correlation of circSNX14 and LATS2 have been confirmed by Pearson correlation in the HCC samples. Collectively, these results reveal a novel role of circSNX14/miR-562/LATS2 axis in regulating the malignant progression of HCC cancer progression, indicating the tumor suppressor role of circSNX14 and its potential as a prognostic biomarker.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49672971","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}
Qianzi Liu, Minxuan Yu, Menglin Liao, Zhiyue Ran, Xiaofeng Tang, Jun Hu, Beiju Su, Gang Fu, Qingqing Wu
{"title":"The ratio of alpha-calcitonin gene-related peptide to substance P is associated with the transition of bone metabolic states during aging and healing","authors":"Qianzi Liu, Minxuan Yu, Menglin Liao, Zhiyue Ran, Xiaofeng Tang, Jun Hu, Beiju Su, Gang Fu, Qingqing Wu","doi":"10.1007/s10735-023-10167-0","DOIUrl":"10.1007/s10735-023-10167-0","url":null,"abstract":"<div><p>Alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP) are functionally correlated sensory neuropeptides deeply involved in bone homeostasis. However, they are usually studied individually rather than as an organic whole. To figure out whether they are interdependent, we firstly recorded the real-time αCGRP and SP levels in aging bone and healing fracture, which revealed a moderate to high level of αCGRP coupled with a low αCGRP/SP ratio in an anabolic state, and a high level of αCGRP coupled with a high αCGRP/SP ratio in a catabolic state, suggesting the importance of αCGRP/SP ratio in driving aging and healing scenarios. During facture healing, increase in αCGRP/SP ratio by adding αCGRP led to better callus formation and faster callus remodeling, while simultaneous addition of αCGRP and SP resulted in hypertrophic callus and delayed remodeling. The characteristics in inflammation and osteoclast activation further confirmed the importance of high αCGRP/SP ratio during catabolic bone remodeling. In vitro assays using different mixtures of αCGRP-SP proved that the osteogenic potential of the mixtures depended mostly on αCGRP, while their effects on osteoclasts and neutrophils relied on both peptides. These results demonstrated that αCGRP and SP were spatiotemporally interdependent. The αCGRP/SP ratio may be more important than the dose of a single neuropeptide in managing age-related and trauma-related bone diseases.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49672972","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":"Intra-articular delivery of geraniol encapsulated by pH/redox-responsive nanogel ameliorates osteoarthritis by regulating oxidative stress and inflammation","authors":"Jun Pan, Youzhi Cai, Chi Zhang, Sanzhong Xu","doi":"10.1007/s10735-023-10163-4","DOIUrl":"10.1007/s10735-023-10163-4","url":null,"abstract":"<div><p>Osteoarthritis (OA) remains a challenging condition due to limited drug bioavailability within the avascular and dense cartilage matrix. This study introduces a pH/redox-responsive nanogel for enhanced delivery of geraniol in OA therapy. We investigated geraniol's role in preventing chondrocyte matrix degradation and designed a pH/redox-responsive nanogel as a delivery platform. Our methods included Western blot, histological staining, and immunohistochemistry. Geraniol treatment reduced Keap1 expression while elevating Nrf2 and HO-1 levels, effectively inhibiting cartilage matrix degradation. The pH/redox-responsive nanogel further enhanced geraniol’s therapeutic impact. Our study demonstrates that geraniol encapsulated within a pH/redox-responsive nanogel mitigates OA by regulating oxidative stress and inflammation. This innovative approach holds potential as an effective OA therapeutic strategy.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}