Promoter analysis and transcriptional regulation of human carbonic anhydrase VIII gene in a MERRF disease cell model

Lo, Che-Min; Ma, Yi‐Shing; Wei, Yau‐Huei; Hsieh, Benjamin Y; Hsieh, Meng‐Hsuan

doi:10.1016/j.abb.2018.01.012

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…The effects of CA on neuronal excitability, the outgrowth of nerve processes, the release of neurotransmitters, mitochondrial energy production, and cell fate are considerable. In early studies, CAVIII was found to be associated with neurodegenerative diseases, including epilepsy, MERRF disease, and spinal cerebellar ataxia (SCA) [6,7].…”

Section: Introductionmentioning

confidence: 99%

Carbonic Anhydrase VIII (CAVIII) Gene Mediated Colorectal Cancer Growth and Angiogenesis through Mediated miRNA 16-5p

et al. 2022

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Carbonic anhydrase VIII (CAVIII) is a member of the CA family, while CA8 is the oncogene. Here we observed increased expression of CAVIII with high expression in colorectal cancer tissues. CAVIII is also expressed in more aggressive types of human colorectal cancer cells. Upregulated CAVIII expression in SW480 cell lines increased vascular endothelial growth factor (VEGF) and reduced miRNA16-5p. Conversely, knockdown of the CAVIII results in VEGF decline by up-regulated miRNA16-5p. Moreover, the collection of different grades of CAVIII expression CRC cells supernatant co-culture with endothelial progenitor cells (EPCs) promotes the ability of tube formation in soft agar and migration in the Transwell experiment, indicating that CAVIII might facilitate cancer-cell-released VEGF via the inhibition of miRNA16-5p signaling. Furthermore, in the xenograft tumor angiogenesis model, knockdown of CAVIII significantly reduced tumor growth and tumor-associated angiogenesis. Taken together, our results prove that the CAVIII/miR-16-5p signaling pathway might function as a metastasis suppressor in CRC. Targeting CAVIII/miR-16-5p may provide a strategy for blocking its metastasis.

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Section: Introductionmentioning

confidence: 99%

Carbonic Anhydrase VIII (CAVIII) Gene Mediated Colorectal Cancer Growth and Angiogenesis through Mediated miRNA 16-5p

et al. 2022

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“…Because the increased mRNA and protein levels of CA8 may indicate altered transcription regulation, we assayed the promoter activity of CA8 in HEK293 stable cells with WT or mutant ataxin‐3. We transfected a luciferase reporter plasmid containing the full‐length of CA8 promoter (Lo et al, ) into HEK293‐MJD26, HEK293‐MJD78, and HEK293‐tMJD78 cells along with a β‐gal vector as a transfection control. As shown in Figure c, the luciferase activity of HEK293‐MJD78 cells was clearly higher than that of HEK293‐MJD26 cells ( p = 0.045), suggesting that CA8 is upregulated at the transcription level in the presence of mutant ataxin‐3.…”

Section: Resultsmentioning

confidence: 99%

“…Even though we have yet to understand the detailed mechanism involved, transcriptional dysregulation has been implicated to play a central role in the SCA3 pathogenesis (Riley & Orr, ). It is likely that mutant ataxin‐3, but not the truncated form, is involved in the transcriptional regulation of hCA8 gene via chromatin binding or interaction with transcriptional regulators (Evert et al, ; Lo et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Protective roles of carbonic anhydrase 8 in Machado–Joseph Disease

Hsieh

Hsieh²,

et al. 2019

J of Neuroscience Research

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Machado–Joseph disease (MJD)/Spinocerebellar ataxia type 3 (SCA3) is an inherited neurodegenerative disease that can lead to a regression of motor coordination and muscle control in the extremities. It is known that expansion of CAG repeats encodes abnormally long polyQ in mutant ataxin‐3, the disease protein. It is also noted that mutant ataxin‐3 interacts with 1,4,5‐trisphosphate receptor type 1 (IP3R1) and induces abnormal Ca2+ release. Previously, we have shown a significant increase in the expression of carbonic anhydrase VIII (CA8) in SK‐N‐SH‐MJD78 cells, which are human neuroblastoma cells overexpressing mutant ataxin‐3 with 78 glutamine repeats. In the current study, we showed the presence of significantly increased CA8 expression in MJD mouse cerebellum in either early or late disease stage, with a gradual decrease in CA8 expression as the MJD mice naturally aged. By immunofluorescence and immunoprecipitation analysis, we also found that CA8 co‐localized and interacted with mutant ataxin‐3 in SK‐N‐SH‐MJD78 cells harboring overexpressed CA8 (SK‐MJD78‐CA8). In addition, we found that SK‐MJD78‐CA8 cells, as well as cerebellar granule neurons (CGNs) of MJD transgenic (Tg) mouse with overexpressed CA8, were more resistant to reactive oxygen species (ROS) stress than the control cells. Importantly, overexpression of CA8 in SK‐MJD78‐CA8 cells and in MJD CGNs rescued abnormal Ca2+ release and caused an increase in cell survival. In summary, we demonstrate the protective function of CA8 in MJD disease models and speculate that the declining expression of CA8 following an initial increased expression may be related to the late onset phenomenon of MJD.

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“…This strongly suggested the involvement of Sp1 in the regulation of CAIII expression. Numerous genes required for cellular function have been demonstrated to be regulated by Sp1 [44,45]. Sp1 may also serve as a transactivator by itself or in conjunction with other recruited co-activators to increase the expression of some particular genes.…”

Section: Sp1 Directly Binds On Multiple Putative Sp1 Sites Of Caiii P...mentioning

confidence: 99%

Transcriptional activation of Carbonic Anhydrase III (CAIII) mediated by SP1

Okuyan,

Köçkar

2024

Preprint

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Many physiological and pathological processes require the expression and control of CAIII. Although the CAIII promoter has not been fully characterized, promoters for other carbonic anhydrase genes in humans have. In this research, we for the first time located and described the human Carbonic anhydrase III gene promoter region. Progressive deletion analysis of the 5′-flanking region of the CAIII gene showed that the CAIII core promoter is mainly restricted to a minimum region of 129 bp. The CAIII gene promoter was discovered to include additional potential binding sites for transcriptional factors including C/EBP and NF-B despite lacking the standard TATA box, according to an investigation of transcriptional factor binding. Furthermore, site-directed mutagenesis assay showed that the proximal Sp1 binding site is required for the essential core promoter activity of the CAIII gene. It was also shown that the CAIII gene was up-regulated by SP1 at the mRNA and protein levels, and this effect was also observed in deletion promoter constructs. Our current study will shed light on further studies on the mechanism that regulates the expression of this important gene.

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Promoter analysis and transcriptional regulation of human carbonic anhydrase VIII gene in a MERRF disease cell model

Cited by 6 publications

References 49 publications

Carbonic Anhydrase VIII (CAVIII) Gene Mediated Colorectal Cancer Growth and Angiogenesis through Mediated miRNA 16-5p

Carbonic Anhydrase VIII (CAVIII) Gene Mediated Colorectal Cancer Growth and Angiogenesis through Mediated miRNA 16-5p

Protective roles of carbonic anhydrase 8 in Machado–Joseph Disease

Transcriptional activation of Carbonic Anhydrase III (CAIII) mediated by SP1

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