{"title":"Circular RNA Sec61 subunit alpha isoform 1 by competitive absorption of microRNA-513a-5p mediates peroxisomal biogenesis factor 5 expression and promotes the malignant phenotype of non-small cell lung cancer.","authors":"Zhe-Ping Duan, Xin-Jiang Yu, Hua-Lin Wei","doi":"10.1002/kjm2.12639","DOIUrl":"https://doi.org/10.1002/kjm2.12639","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are functional RNAs in the development and metabolism of non-small cell lung cancer (NSCLC). Therein, this paper particularly elucidated the circRNA SEC61 subunit alpha isoform 1 (circSEC61A1) in NSCLC has not been fully elucidated. Clinical analysis of circSEC61A1 expression was performed on specimens collected from 51 patients with primary NSCLC, together with patients' survival. Cell experiments were performed after interfering with circSEC61A1, microRNA (miR)-513a-5p, and peroxisomal biogenesis factor 5 (PEX5) expression, respectively, and cell malignant phenotypes and aerobic glycolysis were evaluated, as well as epithelial-to-mesenchymal transition (EMT)-related markers and Wnt/β-catenin pathway. Xenografts experiments studied the performance of circSEC61A1 in vivo. The downstream molecules of circSEC61A1 were searched. Our data demonstrated that circSEC61A1 was upregulated in NSCLC patients, showing an association with poorer survival outcomes. In cell experiments, circSEC61A1 overexpression promoted NSCLC malignant phenotypes, glycolysis, EMT, and Wnt/β-catenin pathway activation, whereas circSEC61A1 underexpression did the opposite. Knockdown of circSEC61A1 limited tumor growth and metastasis. Furthermore, circSEC61A1 could regulate PEX5 expression through competitive absorption of miR-513a-5p. Generally, circSEC61A1 is a potential biomarker for NSCLC, and circSEC61A1 serves tumor-promoting action in the progression of NSCLC.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 4","pages":"326-336"},"PeriodicalIF":3.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9260312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CircTNPO3 promotes hepatocellular carcinoma progression by sponging miR-199b-5p and regulating STRN expression.","authors":"Jing Liu, BingJie Liu","doi":"10.1002/kjm2.12631","DOIUrl":"https://doi.org/10.1002/kjm2.12631","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common primary liver tumor, which seriously threatens human health. CircTNPO3 was up-regulated in HCC tissues. However, the regulatory mechanism of circTNPO3 in HCC was still unclear. We aimed to investigate the circTNPO3 function in the development of HCC. qRT-PCR and Western blot examined gene and protein levels. CCK8, EdU, flow cytometry, and Transwell assays were used to detect cell viability, proliferation, apoptosis, and invasion abilities. Dual-luciferase reporter and RIP assays determined the relationship between circTNPO3, miR-199b-5p, and striatin (STRN). The effect of CircTNPO3 on HCC progress was investigated in vivo. CircTNPO3 and STRN were significantly increased, while miR-199b-5p was repressed in HCC tissues or cells. Afterward, miR-199b-5p was negatively correlated with STRN. circTNPO3 was positively correlated with STRN. Knockdown of circTNPO3 inhibited cell viability, proliferation, invasion, and promoted apoptosis, while circTNPO3 overexpression had the opposite results. Furthermore, miR-199b-5p inhibition could eliminate the regulatory effect of sh-circTNPO3 on the proliferation and apoptosis in HCC cells. CircTNPO3 positively regulated STRN expression by targeting miR-199b-5p. MiR-199b-5p suppressed HCC progression by inhibiting STRN expression. Tumor formation in nude mice showed that knockdown of circTNPO3 significantly inhibited tumor growth and suppressed ki-67 levels. CircTNPO3 promoted HCC progression through regulating STRN expression by sponging miR-199b-5p, which provided a strategy for HCC treatment.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"221-233"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9432659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Sun, Wei-Xing Lu, Hui Li, Ding-Ya Feng, Jing-Xiao Nie
{"title":"Total saponins of Aralia elata (Miq.) Seem. alleviate myocardial ischemia-reperfusion injury by promoting NLRP3-inflammasome inactivation via PI3K/Akt signaling.","authors":"Li Sun, Wei-Xing Lu, Hui Li, Ding-Ya Feng, Jing-Xiao Nie","doi":"10.1002/kjm2.12627","DOIUrl":"https://doi.org/10.1002/kjm2.12627","url":null,"abstract":"<p><p>Total saponins of Aralia elata (Miq.) Seem. (TSAE) have been shown to play a significant role in cardiovascular protection, anti-tumor, liver protection, anti-oxidant stress, and anti-inflammation. However, the specific mechanisms of TSAE in myocardial ischemia-reperfusion injury (MIRI) remain largely elusive. Hearts from male Wistar rats were used to establish the isolated heart MIRI model. Using a multichannel physiological recorder, the whole course heart rate (HR), left ventricular development pressure (LVDP), and maximum rise/decrease rate of left ventricular pressure (±dp/dt<sub>max</sub> ) were recorded. 2,3,5-triphenyl-2H-tetrazolium chloride staining observed the infarct area, while hematoxylin & eosin staining detected pathological changes in myocardial tissue. Creatine kinase, lactate dehydrogenase, total superoxide dismutase, and malondialdehyde concentrations were determined by enzyme-linked immunosorbent assay. Immunohistochemistry, quantitative PCR, and western blot assay were used to assess the amounts of IL-18 and IL-1β, NLR family protein (NLRP3) inflammasome- and apoptosis-related proteins, respectively. Treatment with TSAE or MCC950 (NLRP3-specific inhibitor) significantly reduced the myocardial infarction area, alleviated pathological changes in myocardial tissues, enhanced LVDP and ±dp/dt<sub>max</sub> levels, prevented myocardial oxidative damage, and inhibited NLRP3 inflammasome formation. In addition, TSAE enhanced Akt and GSK3β phosphorylation, and LY29004 co-reperfusion markedly diminished the protective role of TSAE reperfusion on cardiac function, oxidative damage, and inflammatory responses. Collectively, TSAE treatment exhibited a protective effect on I/R-triggered inflammatory responses, cell necrosis, and oxidative stress injury by stimulating PI3K/Akt signaling-mediated NLRP3 inflammasome inhibition.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"290-301"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9448526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical prognosis of surgical resection versus transarterial chemoembolization for single large hepatocellular carcinoma (≥5 cm): A propensity score matching analysis.","authors":"Pei-Min Hsieh, Pojen Hsiao, Yaw-Sen Chen, Jen-Hao Yeh, Chao-Ming Hung, Hung-Yu Lin, Ching-Hou Ma, TaoQian Tang, Yu Wei Huang, Pin-Nan Cheng, Kun-Chou Hsieh, Kuang-Chun Hu, Ming-Jong Bair, Chih-Wen Lin","doi":"10.1002/kjm2.12640","DOIUrl":"https://doi.org/10.1002/kjm2.12640","url":null,"abstract":"<p><p>Favorable prognostic factors and therapeutic strategies are important for patients with single large hepatocellular carcinoma (HCC). This retrospective study aimed to investigate the prognostic factors in patients with single large (≥5 cm) HCC with Child-Pugh (CP) class A patients and to recommend therapeutic strategies. Overall, 298 HCC patients with single and large (≥5 cm) tumors with CP class A, but without distant metastasis and macrovascular invasion were included, and their clinicopathological data, overall survival (OS), and progression-free survival (PFS) were recorded. OS and PFS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. The 298 HCC patients were 79.2% male and median age of 64 years. For the initial treatment, surgical resection (SR) and transarterial chemoembolization (TACE) was 50.8% and 49.2%, respectively. The OS and PFS were significantly higher in patients receiving SR than those receiving TACE before and after PSM. Furthermore, in multivariate analysis, cirrhosis (Hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.35-3.03, p < 0.001, CP class A5/6 [HR: 4.01; 95% CI: 2.43-6.66, p < 0.001], and initial treatment [SR vs. TACE HR = 3.23; 95% CI: 2.13-5.01, p < 0.001]) remained significantly associated with mortality. Moreover, in multivariate analysis, CP class A5/6 (HR: 3.23; 95% CI: 1.89-5.88, p < 0.001), and initial treatment (Resection vs. TACE; HR = 4.17; 95% CI: 1.64-8.33, p = 0.039) remained significantly associated with recurrence. In conclusion, SR was associated with significantly higher OS and PFS rates than TACE before and after PSM for single large HCC patients.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"302-310"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9449065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CircNFIX stimulates the proliferation, invasion, and stemness properties of ovarian cancer cells by enhancing SH3RF3 mRNA stability via binding LIN28B.","authors":"Xiu-Zhang Yu, Bo-Wen Yang, Meng-Yin Ao, Yu-Ke Wu, Hui Ye, Rui-Yu Wang, Ming-Rong Xi, Min-Min Hou","doi":"10.1002/kjm2.12632","DOIUrl":"https://doi.org/10.1002/kjm2.12632","url":null,"abstract":"<p><p>We aimed to study the regulatory roles and mechanism of circular nuclear factor IX (circNFIX) in cancer growth and stemness properties of ovarian cancer (OC). CircNFIX and SH3RF3 levels in OC tissues and cells were tested by quantitative real-time PCR. RNase R treatment quantified circNFIX RNA stability. Molecular interaction among circNFIX, LIN28B, and SH3RF3 was predicted by bioinformatics software and validated through RNA immunoprecipitation (RIP) assay. The gain- or loss-experiments of circNFIX on capabilities of metastasis and stemness in vitro were assessed using Cell Counting Kit-8, Transwell, western blot, and sphere-formation assays. CircNFIX and SH3RF3 were markedly elevated in OC tissues and OC cells. Knocking down circNFIX repressed the proliferation, migration, invasion, and stemness properties of A2780 and SKOV3 cells. The RIP assay verified the direct binding relationship between LIN28B, circNFIX, and SH3RF3. Additionally, overexpression of circNFIX elevated the SH3RF3 expression, while this effect was reversed by LIN28B silence. Rescue experiments demonstrated that the overexpression of SH3RF3 reversed the knockdown of circNFIX on OC cells' proliferation, metastasis, and stemness properties. CircNFIX improved the mRNA stability and translation of SH3RF3 via recruiting LIN28B, thus promoting the proliferation, invasion, and stemness properties of OC cells in vitro.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"234-243"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9078889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hsa_circ_0079480 enhances cell proliferation, migration, and invasion in colorectal cancer through miR-498/ATP5E axis.","authors":"Ruo-Yang Lin, Zhi-Ming Huang","doi":"10.1002/kjm2.12616","DOIUrl":"https://doi.org/10.1002/kjm2.12616","url":null,"abstract":"<p><p>Circular RNAs play critical roles in tumorigenesis. hsa_circ_0079480 was reported to be upregulated in colorectal cancer (CRC). However, its specific molecule in CRC is poorly understood. Hsa_circ_0079480, miR-498, and ATP5E expressions in CRC tissues and CRC cells were determined using quantitative real-time polymerase chain reaction assay. ATP5E protein level was assessed using Western blot. Cell proliferation, migration, and invasion were examined by 3-(4, 5-Dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide assay and Transwell assays, respectively. Dual-luciferase reporter gene assay was performed to analyze the interactions between hsa_circ_0079480, miR-498, and ATP5E. This study results showed that hsa_circ_0079480 and ATP5E expressions were significantly increased in CRC tissues and CRC cells, while miR-498 was downregulated. Hsa_circ_0079480 knockdown dramatically suppressed CRC cell proliferation, migration, and invasion. Meanwhile, it turned out that hsa_circ_0079480 knockdown inhibited CRC tumor growth in vivo. Hsa_circ_0079480 could negatively regulate miR-498 expression by directly targeting miR-498. MiR-498 overexpression dramatically inhibited CRC cell malignant behaviors. miR-498 negatively regulated ATP5E expression by directly binding to ATP5E. ATP5E knockdown suppressed CRC cell malignant behaviors. ATP5E overexpression mitigated the inhibitory effect of hsa_circ_0079480 on CRC cell malignant behaviors. Since hsa_circ_0079480 knockdown inhibited CRC cells malignant behaviors through regulation of the miR-498/ATP5E axis, it can be concluded that hsa_circ_0079480 might have great potential as therapeutic target for CRC.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"209-220"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9449067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adult T-cell acute lymphoblastic leukemia presenting as concurrent viral exanthem-like reaction and palpable purpura.","authors":"Ya-Tang Yang, Feng-Ling Lin","doi":"10.1002/kjm2.12656","DOIUrl":"https://doi.org/10.1002/kjm2.12656","url":null,"abstract":"Leukemia cutis is an extramedullary manifestation of leukemia resulting from direct invasion of leukemic cells into the skin. It most commonly develops in patients with acute myeloid leukemia (AML) and rarely occurs in patients with acute lymphoblastic leukemia (ALL). 1 Here we report a case of an adult case of T-cell ALL (T-ALL) who initially presented with an unusual form of leukemia cutis. A 66-year-old woman without major systemic disease presented with a 1-month history of generalized asymptomatic skin eruptions. The rash initially presented on the lower extremities, and gradually progressed to the trunk. She reported no constitutional symptoms. Physical examination revealed palpable purpuras on the lower extremities (Figure 1A) and blanchable erythematous maculopapules and confluent patches on the trunk (Figure 1B). No lymphadenopathy was detected. A tentative diagnosis of leukocytoclastic vasculitis with concurrent viral exanthem-like eruption was made. Complete blood count and peripheral blood smear showed anemia (hemoglobin 9.9 g/ dl) and leukopenia (total leukocyte count 3.08*106/L) with 28% of blast cells. A bone marrow biopsy was performed, which showed diffuse interstitial infiltrate of blasts (>20%). These cells showed negative staining for myeloperoxidase, CD4, CD8, CD20, and positive staining for terminal deoxynucleotidyl transferase(TdT), CD3, CD5, CD7, CD34, suggesting an infiltrate of precursor T-cells. A skin biopsy of the palpable purpura on the right lower extremity revealed dense der-mal infiltrate of histiocytes and lymphocytes, with some medium-sized atypical mononuclear cells exhibiting high nuclear to cytoplasmic ratio and prominent nucleoli. Nuclear dusts and extravasation","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"311-312"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9120100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR-mediated epigenetic suppression on VGLL4 by DNMT1.","authors":"Jing Zhai, Jun-Feng Jiang, Lei Shi","doi":"10.1002/kjm2.12636","DOIUrl":"https://doi.org/10.1002/kjm2.12636","url":null,"abstract":"<p><p>Much is known about the significance of lycorine, a natural alkaloid, in combating various types of cancer, including breast cancer (BC), but whether it participates in regulating tamoxifen (TAM) resistance and its underlying mechanism remain to be elucidated. Tamoxifen-resistant (TAMR) BC cells were first established by continuously exposed to increasing concentrations of TAM. Levels of targeted gene including HOXD antisense growth-associated lncRNA (HAGLR) and Vestigial like family member 4 (VGLL4) were analyzed by qRT-PCR and western blot, respectively. Cell proliferation ability was assessed by MTT and EdU assays. Flow cytometry was carried out to evaluate the apoptosis. VGLL4 promoter methylation was examined using methylation specific PCR (MSP). The role of HAGLR acting on the expression of VGLL4 via DNA hypermethylation was confirmed by RNA immunoprecipitation (RIP). Here, we reported that lycorine administration reduced the survival ratio of TAMR BC cells, decreased the IC<sub>50</sub> of TAM, and strengthened TAM-induced apoptosis. HAGLR, observed to be highly expressed in TAMR BC cells, was identified to be a downstream effector of lycorine, of which overexpression abolished lycorine-mediated TAMR inhibition. VGLL4 served as a target of HAGLR in regulating lycorine-mediated suppression on tamoxifen resistance of TAMR BC cells. Mechanistically, HAGLR epigenetically suppressed VGLL4 expression via DNA methyltransferase 1 (DNMT1)-mediated DNA hypermethylation. Taken together, our data highlights the pivotal role of lycorine in TAM resistance of BC, which may provide a potential agent for improving the effectiveness and efficacy of BC resistance.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"278-289"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9112730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ZNF655 mediated by LINC01210/miR-124-3p axis promotes the progression of gastric cancer.","authors":"Wei Bo, Xu-Guang Wang, Min Zhang, Zhong Zhang","doi":"10.1002/kjm2.12634","DOIUrl":"https://doi.org/10.1002/kjm2.12634","url":null,"abstract":"<p><p>Gastric cancer (GC) is a common malignant tumor that usually originates from the epithelium of the gastric mucosa. ZNF655 was a suppressor gene of many cancers. However, the mechanism of ZNF655 in GC remains unknown. Quantitative polymerase chain reaction was used to assess the expression of ZNF655, LINC01210, and miR-124-3p. Western blotting was used to monitor ZNF655 protein expression. MTT, clone formation, transwell, and flow cytometry were all used to investigate the functions of GC cells. The interactions between ZNF655, LINC01210, and miR-124-3p were confirmed using the dual-luciferase reporter gene assay and the RIP assay. ZNF655 was highly expressed in GC cells. ZNF655 knockdown reduced GC cell viability, proliferation, migration, invasion, and induced apoptosis. The level of miR-124-3p was significantly reduced in GC cells. Besides, miR-124-3p targeted ZNF655 and inhibited its expression. MiR-124-3p mimics inhibited GC cell progression, but ZNF655 overexpression reversed these effects. Moreover, LINC01210 was found to be highly expressed in GC cells and to be able to sponge miR-124-3p. Furthermore, inhibiting miR-124-3p or increasing ZNF655 could counteract the effects of LINC01210 knockdown on GC cell development. Finally, ZNF655 promoted GC cell progression and was regulated by the LINC01210/miR-124-3p axis.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"200-208"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9174202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis.","authors":"Bin Huang, Yue-Ling Luo, Jun-Ling Huang, Guang-Zhi Li, Shi-Yuan Qiu, Chun-Chun Huang","doi":"10.1002/kjm2.12633","DOIUrl":"https://doi.org/10.1002/kjm2.12633","url":null,"abstract":"<p><p>Hyperglycemia is the most important factor leading to the complications of type 2 diabetes mellitus (T2DM). The primary condition for the treatment of T2DM is to change the glucose and lipid metabolism disorders in the liver and other insulin-sensitive tissues. The current study aims to unearth the potential molecular mechanism of inhibiting liver gluconeogenesis to provide a new theoretical basis for the treatment of T2DM. High glucose (HG) induction of HepG2 cells followed by treatment with sequence-similar family 3 member D (FAM3D). Dual specificity phosphatases 1 (DUSP1), zinc finger protein 36 (ZFP36), salt-induced kinase 1 (SIK1), p-SIK1, posphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene and protein expression level were detected by quantitative real-time polymerase chain reaction and western blot. The PEPCK and G6Pase activities were detected by enzyme linked immunosorbent assay. Glucose production assay to determine glucose content. The RNA binding protein immunoprecipitation assay was used to detect the binding of ZFP36 to SIK1. FAM3D facilitated the expression of DUSP1 but suppressed the expression of gluconeogenesis-related factors in an HG environment. The expression of ZFP36 was up-regulated in an HG environment. ZFP36 could reverse the inhibition of gluconeogenesis caused by FAM3D. HG-induced upregulation of ZFP36 was downregulated by overexpression of DUSP1. ZFP36 bound to SIK1, and downregulation of ZFP36 promoted SIK1 expression and inhibits gluconeogenesis. Our study demonstrated FAM3D inhibited gluconeogenesis through the DUSP1/ZFP36/SIK1 axis in an HG environment, which provided a new theoretical basis for exploring the pathogenesis and treatment strategy of T2DM.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":"39 3","pages":"254-265"},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9448581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}