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991.
Dao-Chen Lin Chi-Yu Huang Wei-Hsin Ting Fu-Sung Lo Chiung-Ling Lin Horng-Woei Yang Tzu-Yang Chang Chao-Hsu Lin Yao-Wei Tzeng Wan-Syuan Yang Yue-Li Juang Yann-Jinn Lee 《生物化学与生物物理学报:疾病的分子基础》2019,1865(2):428-433
Monogenic diabetes is caused by mutations that reduce β-cell function. While Sanger sequencing is the standard method used to detect mutated genes. Next-generation sequencing techniques, such as whole exome sequencing (WES), can be used to find multiple gene mutations in one assay. We used WES to detect genetic mutations in both permanent neonatal (PND) and type 1B diabetes (T1BD).A total of five PND and nine T1BD patients were enrolled in this study. WES variants were assessed using VarioWatch, excluding those identified previously. Sanger sequencing was used to confirm the mutations, and their pathogenicity was established via the literature or bioinformatic/functional analysis. The PND and T1BD patients were diagnosed at 0.1–0.5 and 0.8–2.7?years of age, respectively. Diabetic ketoacidosis was present at diagnosis in 60% of PND patients and 44.4% of T1BD patients. We found five novel mutations in five different genes. Notably, patient 602 had a novel homozygous missense mutation c.1295C?>?A (T432?K) in the glucokinase (GCK) gene. Compared to the wild-type recombinant protein, the mutant protein had significantly lower enzymatic activity (2.5%, p?=?0.0002) and Vmax (1.23?±?0.019 vs. 0.33?±?0.016, respectively; p?=?0.005). WES is a robust technique that can be used to unravel the etiologies of genetically heterogeneous forms of diabetes. Homozygous inactivating mutations of the GCK gene may have a significant role in PND pathogenesis. 相似文献
992.
Feng Guo Chengchun Tang Bo Huang Lifei Gu Jun Zhou Zongyang Mo Chang Liu Yuqing Liu 《Molecules and cells》2022,45(3):122
The aim of this study was to investigating whether lncRNA H19 promotes myocardial fibrosis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis. Patients with atrial fibrillation (AF) and healthy volunteers were included in the study, and their biochemical parameters were collected. In addition, pcDNA3.1-H19, si-H19, and miR-29a/b-3p mimic/inhibitor were transfected into cardiac fibroblasts (CFs), and proliferation of CFs was detected by MTT assay. Expression of H19 and miR-29a/b-3p were detected using real-time quantitative polymerase chain reaction, and expression of α-smooth muscle actin (α-SMA), collagen I, collagen II, matrix metalloproteinase-2 (MMP-2), and elastin were measured by western blot analysis. The dual luciferase reporter gene assay was carried out to detect the sponging relationship between H19 and miR-29a/b-3p in CFs. Compared with healthy volunteers, the level of plasma H19 was significantly elevated in patients with AF, while miR-29a-3p and miR-29b-3p were markedly depressed (P < 0.05). Serum expression of lncRNA H19 was negatively correlated with the expression of miR-29a-3p and miR-29b-3p among patients with AF (rs = –0.337, rs = –0.236). Moreover, up-regulation of H19 expression and down-regulation of miR-29a/b-3p expression facilitated proliferation and synthesis of extracellular matrix (ECM)-related proteins. SB431542 and si-VEGFA are able to reverse the promotion of miR-29a/b-3p on proliferation of CFs and ECM-related protein synthesis. The findings of the present study suggest that H19 promoted CF proliferation and collagen synthesis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis, and provide support for a potential new direction for the treatment of AF. 相似文献
993.
Mg2+依赖性蛋白磷酸酶1δ(protein phosphatase magnesium-dependent 1δ,PPM1D)作为肝癌潜在的预后标志物和治疗靶点,其致癌机制和预后价值仍未完全阐明。为了全面认识PPM1D,使用生物信息学方法,对PPM1D蛋白的序列同源性、组织表达、亚细胞定位、理化性质、空间结构及蛋白质相互作用网络进行分析。结果表明:人PPM1D基因编码605个氨基酸组成的多肽,与物种进化程度一致,属于PP2C蛋白超家族,是碱性不稳定的亲水蛋白,无信号肽和跨膜区域;PPM1D蛋白主要定位于细胞核内,其主要二级结构为随机卷曲,存在磷酸化、乙酰化、甲基化和泛素化位点,与PPM1D相互作用的蛋白主要是细胞周期检查点蛋白和细胞损伤修复相关蛋白。根据分析结果阐述了PPM1D蛋白与癌症的相关性以及PPM1D蛋白作为癌症标志物的理论基础,为进一步研究该蛋白及其参与的信号通路提供一定的借鉴和参考。 相似文献
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997.
Longfei Li Zhimin Li Jingming Qu Xiangju Wei Feng Suo Jilei Xu Xiucheng Liu Chang Chen Shiying Zheng 《Journal of cellular and molecular medicine》2022,26(5):1402
Abnormally expressed long non‐coding RNAs (lncRNAs) have been recognized as potential diagnostic biomarkers or therapeutic targets in non‐small cell lung cancer (NSCLC). The role of the novel lnc‐CYB561‐5 in NSCLC and its specific biological activity remain unknown. In this study, lncRNAs highly expressed in NSCLC tissue samples compared with paired adjacent normal tissue samples and atypical adenomatous hyperplasia were identified by RNA‐seq analysis. Lnc‐CYB561‐5 is highly expressed in human NSCLC and is associated with a poor prognosis in lung adenocarcinoma. In vivo, downregulation of lnc‐CYB561‐5 significantly decreases tumour growth and metastasis. In vitro, lnc‐CYB561‐5 knockdown treatment inhibits cell migration, invasion and proliferation ability, as well as glycolysis rates. In addition, RNA pulldown and RNA immunoprecipitation (RIP) assays show that basigin (Bsg) protein interacts with lnc‐CYB561‐5. Overall, this study demonstrates that lnc‐CYB561‐5 is an oncogene in NSCLC, which is involved in the regulation of cell proliferation and metastasis. Lnc‐CYB561‐5 interacts with Bsg to promote the expression of Hk2 and Pfk1 and further lead to metabolic reprogramming of NSCLC cells. 相似文献
998.
Chong Zhou Xi He Chang Tong Honghui Li Caifeng Xie Yudong Wu Lieliang Wang Xiaohua Yan Daya Luo Yunpeng Tang Zhongman Cheng Xiangyang Xiong 《International journal of biological sciences》2022,18(4):1363
Cancer-associated adipocytes (CAAs), which are adipocytes transformed by cancer cells, are of great importance in promoting the progression of breast cancer. However, the underlying mechanisms involved in the crosstalk between cancer cells and adipocytes are still unknown. Here we report that CAAs and breast cancer cells communicate with each other by secreting the cytokines leukemia inhibitory factor (LIF) and C-X-C subfamily chemokines (CXCLs), respectively. LIF is a pro-inflammatory cytokine secreted by CAAs, which promotes migration and invasion of breast cancer cells via the Stat3 signaling pathway. The activation of Stat3 induced the secretion of glutamic acid-leucine-arginine (ELR) motif CXCLs (CXCL1, CXCL2, CXCL3 and CXCL8) in tumor cells. Interestingly, CXCLs in turn activated the ERK1/2/NF-κB/Stat3 signaling cascade to promote the expression of LIF in CAAs. In clinical breast cancer pathology samples, the up-regulation of LIF in paracancerous adipose tissue was positively correlated with the activation of Stat3 in breast cancer. Furthermore, we verified that adipocytes enhanced lung metastasis of breast cancer cells, and the combination of EC330 (targeting LIF) and SB225002 (targeting C-X-C motility chemokine receptor 2 (CXCR2)) significantly reduced lung metastasis of breast cancer cells in vivo. Our findings reveal that the interaction of adipocytes with breast cancer cells depends on a positive feedback loop between the cytokines LIF and CXCLs, which promotes breast cancer invasion and metastasis. 相似文献
999.
Fei Liu Qianying Han Ting Zhang Fen Chang Jingcheng Deng Xiaotian Huang Weiping Wang Yongjie Xu Qin Li Luzheng Xu Bo Zhang Wentong Li Li Li Yanrong Su Yang Li Genze Shao 《International journal of biological sciences》2022,18(4):1434
BRCA1 is frequently down-regulated in breast cancer, the underlying mechanism is unclear. Here we identified DCAF8L1, an X-linked gene product, as a DDB1-Cullin associated Factor (DCAF) for CUL4 E3 ligases to target BRCA1 and BARD1 for proteasomal degradation. Forced expression of DCAF8L1 caused reduction of BRCA1 and BARD1, and impaired DNA damage repair function, conferring increased sensitivity to irradiation and DNA damaging agents, as well as Olaparib, a PARPi anticancer drug; while depletion of DCAF8L1 restored BRCA1 and suppressed the growth of its xenograft tumors. Furthermore, the expression of DCAF8L1 was induced in human H9 ES cells during transition from primed to naïve state when Xi chromosome was reactivated. Aberrant expression of DCAF8L1 was observed in human breast fibroadenoma and breast cancer. These findings suggest that CRL4DCAF8L1 is an important E3 ligase that may participate in the development of breast cancer, probably through regulating the stability of BRCA1 and BARD1 tumor suppressor, linking BRCA1 and X chromosome inactivation to breast carcinogenesis. 相似文献
1000.
该文旨在探讨干扰素-β(interferon-β,IFN-β)在肺炎链球菌(Streptococcus pneumoniae,S.pn)感染早期对宿主炎症免疫的影响.使用外源重组IFN-β蛋白(recombinant IFN-β,rIFN-β)预处理WT小鼠及其腹腔渗出巨噬细胞(peritoneal exudate m... 相似文献