Connexin subtype expression during oral carcinogenesis: A pilot study in patients with oral squamous cell carcinoma

Brockmeyer, Phillipp; Hemmerlein, Bernhard; Jung, Klaus; Fialka, Florian; Brodmann, Tobias; Gruber, Rudolf; Schliephake, Henning; Kramer, Franz‐Josef

doi:10.3892/mco.2015.685

Cited by 5 publications

(7 citation statements)

References 32 publications

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“…connexin 43 (cx43), a member of the connexins family, is most abundantly expressed in the cardiac muscle (7). cx43 has been demonstrated to serve a role in a number of diseases, including oral squamous cell carcinoma, pancreatic cancer, prostate cancer, acute myeloid leukemia, myocardial edema, vascular restenosis and Parkinson's disease (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). cx43 is primarily a fast, low-resistance pathway that regulates electrical conduction between cardiomyocytes, coordinates mechanical and electrical activities of cardiac muscle and controls the conduction velocity of impulses to ensure that myocardial electromechanical activities are synchronized (18).…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

et al. 2018

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Atrial fibrillation (AF) is the most common arrhythmia reported in clinical practice. Connexin 43 (Cx43) is a member of the connexin protein family, which serves important roles in signal transduction in vivo. The aim of the present study was to investigate the role of Cx43 in the induction and maintenance of atrial fibrillation by using an animal model of sympathomimetic atrial fibrillation. Cx43 was successfully knocked down in the myocardium with gene‑specific small interfering (si)RNA via lentiviral infection. A total of 25 dogs were randomly and evenly divided into five groups: Normal (N), rapid atrial pacing (RAP), isoproterenol (ISO) + RAP, RAP + Cx43 siRNA and ISO + RAP + Cx43 siRNA. The mRNA and protein levels, as well as the distribution of Cx43 on the cell membrane, were gradually decreased in each group compared with the N group following treatment (P<0.05). The induction rate of the atrial effective refractory period was not significantly affected in the RAP and RAP + Cx43 siRNA groups, whereas it was significantly reduced in the ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with the N group (P<0.05). The induction rate of AF was gradually increased in the RAP + Cx43 siRNA, ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with the N group (P<0.05). The expression of nerve growth factor (NGF) and tyrosine hydroxylase (TH) was gradually increased in the ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with their respective controls (RAP and RAP + Cx43 siRNA groups, respectively). However, no significant difference in the levels of NGF and TH was observed between the RAP, RAP + Cx43 siRNA, ISO + RAP and ISO + RAP + Cx43 siRNA groups. The mitochondrial morphology in each group was notably altered compared with the N group. The mitochondrial reactive oxygen species production and apoptotic index were gradually increased in each group compared with the N group (P<0.05). The results of the present study suggest that Cx43 reduces susceptibility to AF. Downregulation of Cx43 mediates the induction and maintenance of sympathetic AF.

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Section: Introductionmentioning

confidence: 99%

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

et al. 2018

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“…On the other hand, the higher frequency of the mutated G allele in the population identifies a population profile different from that described in countries such as Brazil for this SNP ( 18 ).…”

Section: Discussionmentioning

confidence: 69%

“…These results match those of Brockmeyer et al . in samples of OSCC patients ( 18 ). Studies in breast cancer showed that silencing Cx43 expression contributes to breast carcinogenesis, due to enhanced cell proliferation, lost cell polarity, misorientation of the mitotic spindle, and lost multilayer architecture of epithelial tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Cx43 is one of the potential biomarkers of tumorigenesis in the oral mucosa ( 18 ). Our results showed that this protein was not expressed in the membrane of cells from OSCC patient samples.…”

Section: Discussionmentioning

confidence: 99%

“…The reaction with all reagents excluding the template DNA was used as a negative control. The GJA1 C/G product (110 bp) was digested with Hae III (Thermo Fisher Scientific, Inc) at 37 °C for 3h, and the polymorphisms were determined as CC (110 bp), CG (57, 53, and 110 bp), or GG (53 and 57 bp) ( 18 ). The reaction having all the reagents excluding the genomic DNA was used as a negative control.…”

Section: Methodsmentioning

confidence: 99%

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Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Segura¹,

Secchi²,

Galíndez³

et al. 2022

Med Oral

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Background To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patients with oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredicTable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax, E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition. Material and Methods A cross-sectional study using genomic DNA and biopsy samples extracted from the oral mucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, Universidad Nacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797 by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test was applied to analyze immunostaining between controls/cases ( p <0.05 was set for statistical significance). Results GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation to CC “healthy” genotype ( p =0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in 75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis ( p =0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherin markers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, and Bax immunomarker was diminished in OSCC. Conclusions We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, which modifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G of GJA1rs12197797 could be at risk of developing OSCC. Key words: Cx43, E-cadherin, Ki67, Bax, Bcl-2, immunostaining expression profile, GJA1 rs12197797 genotyping.

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Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions

Yasarbas,

Inal,

Yildirim

et al. 2024

Front. Physiol.

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The epidermis, the outermost layer of the skin, serves as a protective barrier against external factors. Epidermal differentiation, a tightly regulated process essential for epidermal homeostasis, epidermal barrier formation and skin integrity maintenance, is orchestrated by several players, including signaling molecules, calcium gradient and junctional complexes such as gap junctions (GJs). GJ proteins, known as connexins facilitate cell-to-cell communication between adjacent keratinocytes. Connexins can function as either hemichannels or GJs, depending on their interaction with other connexons from neighboring keratinocytes. These channels enable the transport of metabolites, cAMP, microRNAs, and ions, including Ca2+, across cell membranes. At least ten distinct connexins are expressed within the epidermis and mutations in at least five of them has been linked to various skin disorders. Connexin mutations may cause aberrant channel activity by altering their synthesis, their gating properties, their intracellular trafficking, and the assembly of hemichannels and GJ channels. In addition to mutations, connexin expression is dysregulated in other skin conditions including psoriasis, chronic wound and skin cancers, indicating the crucial role of connexins in skin homeostasis. Current treatment options for conditions with mutant or altered connexins are limited and primarily focus on symptom management. Several therapeutics, including non-peptide chemicals, antibodies, mimetic peptides and allele-specific small interfering RNAs are promising in treating connexin-related skin disorders. Since connexins play crucial roles in maintaining epidermal homeostasis as shown with linkage to a range of skin disorders and cancer, further investigations are warranted to decipher the molecular and cellular alterations within cells due to mutations or altered expression, leading to abnormal proliferation and differentiation. This would also help characterize the roles of each isoform in skin homeostasis, in addition to the development of innovative therapeutic interventions. This review highlights the critical functions of connexins in the epidermis and the association between connexins and skin disorders, and discusses potential therapeutic options.

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Connexin subtype expression during oral carcinogenesis: A pilot study in patients with oral squamous cell carcinoma

Cited by 5 publications

References 32 publications

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions

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