GENOMIC PLANT DNA KIT-96 WELL
- Known as:
- GENOMIC PLANT Desoxyribonucleic acid KIT-96 WELL
- Catalog number:
- IB47270
- Category:
- -
- Supplier:
- IBISCI
- Gene target:
- GENOMIC PLANT DNA KIT-96 WELL
Related genes to: GENOMIC PLANT DNA KIT-96 WELL
- Gene:
- LRRC8A NIH gene
- Name:
- leucine rich repeat containing 8 VRAC subunit A
- Previous symbol:
- LRRC8
- Synonyms:
- KIAA1437, FLJ10337, SWELL1
- Chromosome:
- 9q34.11
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-26
- Date modifiied:
- 2019-04-23
Related products to: GENOMIC PLANT DNA KIT-96 WELL
Related articles to: GENOMIC PLANT DNA KIT-96 WELL
- Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl-sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke. - Source: PubMed
Publication date: 2024/05/08
Lu Feng-TingHuang Cheng-CuiLai Wen-YiYang Gui-YongLiang Zhu-JunZhang Zi-YiChokshi TanviGuo Kai-MinTang Yu-BoChen YuanYang Zhong-HanLiang Si-JiaPang Rui-PingZhou Jia-GuoGuan Yong-YuanLv Xiao-FeiMa Ming-Ming - DNA sensing is important for antiviral immunity. The DNA sensor cGAS synthesizes 2'3'-cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which induces innate immunity. cGAMP not only activates STING in the cell where it is produced but cGAMP also transfers to other cells. Transporters, channels, and pores (including SLC19A1, SLC46A2, P2X7, ABCC1, and volume-regulated anion channels (VRACs)) release cGAMP into the extracellular space and/or import cGAMP. We report that infection with multiple human viruses depletes some of these cGAMP conduits. This includes herpes simplex virus 1 (HSV-1) that targets SLC46A2, P2X7, and the VRAC subunits LRRC8A and LRRC8C for degradation. The HSV-1 protein UL56 is necessary and sufficient for these effects that are mediated at least partially by proteasomal turnover. UL56 thereby inhibits cGAMP uptake via VRAC, SLC46A2, and P2X7. Taken together, HSV-1 antagonizes intercellular cGAMP transfer. We propose that this limits innate immunity by reducing cell-to-cell communication via the immunotransmitter cGAMP. - Source: PubMed
Publication date: 2024/04/22
Blest Henry T WRedmond AlexanderAvissar JedBarker JakeBridgeman AnneFowler GerissaChauveau LiseHertzog JonnyVendrell IolandaFischer RomanIversen Marie BJing LichenKoelle David MPaludan Søren RKessler Benedikt MCrump Colin MRehwinkel Jan - Human endogenous retroviruses (HERVs) are the remnants of ancient retroviral infections integrated into the human genome. Although most HERVs are silenced or rendered inactive by various regulatory mechanisms, they retain the potential to influence the nearby genes. We analyzed the regulatory map of 91 HERV-Ks on neighboring genes in human breast cancer and investigated the impact of HERV-Ks on the tumor microenvironment (TME) and prognosis of breast cancer. Nine RNA-seq datasets were obtained from GEO and NCBI SRA. Differentially expressed genes and HERV-Ks were analyzed using DESeq2. Validation of high-risk prognostic candidate genes using TCGA data. These included Overall survival (multivariate Cox regression model), immune infiltration analysis (TIMER), tumor mutation burden (maftools), and drug sensitivity analysis (GSCA). A total of 88 candidate genes related to breast cancer prognosis were screened, of which CD48, SLAMF7, SLAMF1, IGLL1, IGHA1, and LRRC8A were key genes. Functionally, these six key genes were significantly enriched in some immune function-related pathways, which may be associated with poor prognosis for breast cancer (p = 0.00016), and the expression levels of these genes were significantly correlated with the sensitivity of breast cancer treatment-related drugs. Mechanistically, they may influence breast cancer development by modulating the infiltration of various immune cells into the TME. We further experimentally validated these genes to confirm the results obtained from bioinformatics analysis. This study represents the first report on the regulatory potential of HERV-K in the neighboring breast cancer genome. We identified three key HERV-Ks and five neighboring genes that hold promise as novel targets for future interventions and treatments for breast cancer. - Source: PubMed
Publication date: 2024/02/22
Liang BoyingYan TengyueWei HuilinZhang DieLi LanxiangLiu ZengjingLi WenZhang YuluanJiang NiliMeng QiuxiaJiang GuiyangHu YanlingLeng Jing - Colorectal cancer (CRC) has been the third most common malignancy and the second cause of cancer-related mortality. As the core of volume-sensitive chloride currents, leucine-rich repeat-containing 8A (LRRC8A) contributes to tumor progression but is not consistent, especially for whom the roles in colon carcinoma metastasis were not fully elucidated. Herein, LRRC8A proteins were found highly expressed in hematogenous metastasis from human colorectal cancer samples. The oxaliplatin-resistant HCT116 cells highly expressed LRRC8A, which was related to impaired proliferation and enhanced migration. The over-expressed LRRC8A slowed proliferation and increased migration ex vivo and in vivo. The elevated LRRC8A upregulated the focal adhesion, MAPK, AMPK, and chemokine signaling pathways via phosphorylation and dephosphorylation. Inhibition of LRRC8A impeded the TNF-α signaling cascade and TNF-α-induced migration. LRRC8A binding to PIP5K1B regulated the PIP2 formation, providing a platform for LRRC8A to mediate cell signaling transduction. Importantly, LRRC8A self-regulated its transcription via NF-κB1 and NF-κB2 pathways and the upregulation of NIK/NF-κB2/LRRC8A transcriptional axis was unfavorable for colon cancer patients. Collectively, our findings reveal that LRRC8A is a central mediator in mediating multiple signaling pathways to promote metastasis and targeting LRRC8A proteins could become a potential clinical biomarker-driven treatment strategy for colon cancer patients. - Source: PubMed
Publication date: 2024/02/11
Zhang HaifengLiu RongJing ZhenghuiLi ChunyingFan WentaoLi HouliLi HongbingRen JieCui ShiyuZhao WenbaoYu LeiBai YuhuiLiu ShujingFang ChunluYang WenqiWei YuanLi LiangmingPeng Shuang - - Source: PubMed
Publication date: 2024/01/05
Wang YumanSun ZaiqiaoPing JiemingTang JianlongHe BoxiaoChang TedingZhou QianYuan ShijieTang ZhaohuiLi XinLu YanHe RanHe XimiaoLiu ZhengYin LeiWu Ning