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Background: This study aimed to identify a candidate gene associated with paclitaxel (PTX) resistance and to evaluate functionally its biological role in the PTX-resistant head and neck squamous cell carcinoma (HNSCC) cell lines and clinical specimens., Methods: Microarray data series containing samples of different types of cancers resistant to PTX were analyzed and then a candidate gene associated with PTX resistance was identified using various bioinformatics tools. After the suppression of the target gene expression, changes in cell viability and colony-forming ability were evaluated in PTX-resistant FaDu and SCC-9 cell lines., Results: Bioinformatics analyses of upregulated genes in PTX-resistant cancer cells indicated that OAS3 was associated with PTX resistance. The downregulation of OAS3 expression significantly reduced the viability and colony-forming capacity of PTX-resistant SCC-9 cells by inducing apoptosis and cell cycle arrest at G0/G1 phase., Conclusions: The therapeutic targeting of OAS3 may resensitize PTX-resistant HNSCC cells with high OAS3 expression to PTX treatment., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive neoplasms, which requires more effective prevention and treatment modalities. Previous studies found that protein O-fucosyltransferase 1 (POFUT1) upregulation promotes carcinogenesis, although the potential roles, underlying molecular mechanisms, and biological implications of POFUT1 in HNSCC were not investigated. In this study, in silico analyses referred POFUT1 as a potential oncogene in HNSCC. Further analysis of tumor and normal tissue samples as well as HNSCC cells with quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry showed significant overexpression of POFUT1 in HNSCC clinical tumor tissue specimens and cell lines compared to corresponding controls. In vitro investigations revealed that overexpression of POFUT1 promoted phenotypes associated with cancer aggressiveness and its knockdown in HNSCC cells suppressed those phenotypes. Further xenograft experiments demonstrated that POFUT1 is an oncogene in vivo for HNSCC. Immunohistochemical analysis with human clinical samples and cancer cell-dorsal root ganglion ex-vivo coculture model showed that deregulation of POFUT1 is involved in the perineural invasion of HNSCC cells. These results suggest POFUT1 expression as a potential prognostic marker for patients with head and neck cancer and highlight its potential as a target for HNSCC therapy, although more molecular clues are needed to better define the functions of POFUT1 related to HNSCC carcinogenesis., (© 2023 International Federation of Cell Biology.)

Purpose: Development of chemoresistance is one of the major obstacles to the treatment of head and neck squamous cell carcinoma (HNSCC). The PI3K/Akt pathway, involved in drug resistance, has been found to be overactivated in > 90% of HNSCCs. Aberrant activation of the FGF receptors (FGFRs) has been reported to cause overactivation of the PI3K/Akt pathway and to be associated with the maintenance of stem cell features, which is controlled via SOX2 expression. In this study, we aimed at investigating the potential of using AZD4547, an orally bioavailable FGFR inhibitor, to overcome taxol-resistance by targeting the FGFR/Akt/SOX2 axis in HNSCC., Methods: We initially evaluated FGFR2 and SOX2 expression using in silico tools. We analyzed the FGFR/Akt/SOX2 axis in normal/tumor tissue pairs and in recombinant FGF2 treated HNSCC cells. Next, we explored the effects of AZD4547 alone and in combination with taxol on the proliferation, migration and colony forming capacities of parental/taxol-resistant cells using in vitro models., Results: We found that the p-FGFR, p-AKT, p-GSK-3β and SOX2 expression levels were higher in tumor tissues than in its corresponding normal tissues, and that AZD4547 effectively suppressed the expression of FGFR and its downstream targets in recombinant FGF2 treated HNSCC cells. We also found that AZD4547 diminished the viability, migration and colony forming capacity of HNSCC cells, and that co-treatment with taxol potentiated the impact of taxol on these cells. Finally, we found that AZD4547 inhibited the overexpressed FGFR/Akt/SOX2 axis and profoundly suppressed cancer-related phenotypes in taxol-resistant HNSCC cells., Conclusion: From our data we conclude that AZD4547 may increase the impact of taxol during HNSCC treatment. We suggest AZD4547 as a therapeutic agent to overcome taxol-resistance., (© 2021. Springer Nature Switzerland AG.)

Daucus carota L. ssp. major (DCM) plant is widely used in traditional medicine to treat some types of cancer and various diseases. Therefore, we evaluated the biological activities of this plant to define its effects against prostate cancer (PCa), Alzheimer's disease (AD), oxidation, and diabetes mellitus (DM) as well as identified its phenolic composition. To determine the anti-cancer properties of the plant extract, we treated PCa cells with the extract at a concentration range of 0.25, 0.5, 1, 2, and 4 mg/ml. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. As a result of precise measurements at the millimolar level, it was observed that the plant extract showed an effective inhibition (IC 50 ) against glutathione S-transferase (GST; 12.84 mM), acetyl cholinesterase (AChE; 15.07 mM), and α-Gly (11.75 mM) enzymes when compared with standard inhibitors. Antioxidant activities of DCM methanol extract were determined via two well-known in vitro techniques. The extracts showed antioxidant activities against the DPPH and ABTS + . The LC-ESI-MS/MS was used to determine the phenolic compounds of methanol extract from DCM. Chlorogenic acid (2,089.096 µg/g), shikimic acid (193.14 µg/g), and coumarin (113.604 µg/g) were characterized as major phenolic compounds. In addition, the interactions of chlorogenic acid, chrysin, coumarin, and shikimic acid with the used three enzymes have been calculated using molecular docking simulation. PRACTICAL APPLICATIONS: Plant natural phenolic compounds have protective effects such as anti-inflammatory, antioxidant, anticarcinogen, and enzyme inhibitory. Therefore, it has an important place in the food and pharmaceutical industry. The present study aims to reveal the enzyme inhibitory, antioxidant, and anticarcinogenic properties of the Daucus carota ssp. Major (DCM) plant extract. Significant results were obtained against the PC3 cells compared to normal PNT1a prostate epithelial cells. DCM extract demonstrated considerable antioxidant activity and inhibitory potential on used metabolic enzymes. These biological effects are thought to have a relationship with rich chemical composition., (© 2021 Wiley Periodicals LLC.)

Prostate cancer (PCa) is one of the most prevalent cancer types among males. Differential expression of microRNAs is associated with various cancers including PCa. Although mature microRNAs are preferentially located in the cytoplasm, several studies identified mature human microRNAs in purified nuclei and miR-145 has been found to be predominantly expressed in the nuclei of benign tissues compared to tumor lesions. However, the nuclear functions of miR-145 are yet limited. Here, we aimed at investigating the inductive role of miR-145 on the expression of Semaphorin 3A (SEMA3A) in PCa cell lines. To study the regulatory potential of miR-145 in the transcriptional level in PCa, we overexpressed miR-145 in PC3 and DU145 cells, and confirmed its upregulation by quantitative-real-time-PCR. Then we investigated the tumor suppressor potential of miR-145 upon inducing SEMA3A expression using cell viability assay, western blot analysis, Chromatin Immunoprecipitation assay and luciferase reporter assay. Our results revealed that p53, miR-145, and SEMA3A expressions are significantly downregulated in PC3 and DU145 cells compared to nontumorigenic prostate epithelial PNT1a cells. miR-145 overexpression in PCa cells induced the expression of SEMA3A at both messenger RNA and protein levels. Furthermore, increased miR-145 expression enriched RNA Pol-II antibody on the promoter of SEMA3A and induced luciferase activity controlled by SEMA3A promoter. In this study, we showed that the functions of miR-145 are not limited to gene silencing, and found that it may lead to changes in gene expression in the transcriptional level., (© 2021 International Federation for Cell Biology.)

Background: Major milestones of head and neck carcinogenesis have been associated with various genetic abnormalities; however, a clear picture of the molecular networks deregulated during the carcinogenesis of head and neck squamous cell carcinoma (HNSC) has not yet completely revealed., Methods: In this study, we used in silico tools and online data sets to evaluate the underlying reasons for the expressional changes of genes residing within the chromosome 3q and to help understanding their contributions to HNSC carcinogenesis., Results: We found that 13 of 20 most upregulated genes in HNSC are localized to 3q. Further analysis revealed a gene signature consisting of DHX36, OPA1, and SENP2, which showed significant correlation in HNSC samples and potentially be deregulated through similar mechanisms including DNA amplification, transcriptional, and posttranscriptional regulation., Conclusions: Considering our findings, we suggest DHX36, OPA1, and SENP2 genes as overexpressed in HNSC tumors and that might be concurrently involved in HNSC carcinogenesis, tumor progression, and induction of angiogenic pathways., (© 2020 Wiley Periodicals LLC.)

Purpose: Peri-implantitis, a potentially progressive disease that occurs in patients with dental implants, is more aggressive than periodontal lesions, which makes the prevention of peri-implantitis an important priority. Due to problems in the early detection of peri-implantitis, there is an urgent need for discovering novel biologic molecules with the ability of early diagnosis. The goal of this study was to profile the microRNA content of saliva samples collected from patients with titanium-aluminum-vanadium alloy dental implants who experienced peri-implantitis and to find potential diagnostic markers for detection of this disease., Materials and Methods: The microRNA expression profiles of eight saliva samples (four collected from patients with peri-implantitis, four collected from patients who have successful implants) were investigated, and the deregulation of select microRNAs was further confirmed using quantitative polymerase chain reaction., Results: The expressions of 179 microRNAs were found as deregulated in the saliva of peri-implantitis patients in comparison to controls. Then, downregulation of miR-4484 was confirmed in the saliva of peri-implantitis patients in a larger validation cohort. Also, 40% of non-peri-implantitis patients and 78% of peri-implantitis patients had significantly decreased miR-4484 expression in saliva samples collected after 4 to 6 months subsequent to implant placement compared with samples collected before implant placement., Conclusion: Considering these findings, microRNA content of saliva might be proposed as a plausible source for the early diagnosis of peri-implantitis, where miR-4484 might serve as an encouraging early diagnostic biomarker.

Objectives: In this study, we aimed at investigating the expressions of miR-145 and its well-characterized direct targets on carboplatin treatment., Study Design: Laboratory study., Methods: The effect of carboplatin and miR-145 on the proliferative capacity of head and neck squamous cell carcinoma cells was evaluated using Cell Viability Detection Kit-8. Expressions of miR-145 and its targets were evaluated using quantitative real-time polymerase chain reaction on carboplatin treatment and p53 inhibition. Western blot was used to measure the levels of p53 and its acetylated versions in cells treated with carboplatin and/or pifithrin-α., Results: We demonstrated that carboplatin induced the expression of miR-145 in a dose-dependent manner and suppressed the expressions of miR-145 direct targets. In addition, we showed that inhibition of p53 by pifithrin-α in carboplatin-treated cells reduced miR-145 expression and reversed the suppression of miR-145 direct targets., Conclusions: Considering all these findings together, one of the proposed mechanisms of carboplatin to kill cells might be the induction of miR-145 and deregulation of its targets in parallel, via p53 activation, which happens through carboplatin's DNA-damaging property. To the best of our knowledge, these findings are the first to reveal the relationship between carboplatin and miR-145 in cancer cells., Level of Evidence: NA Laryngoscope, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Oral cancer (OC), which is the most common form of head and neck cancers, has one of the lowest (~50%) overall 5-year survival rates. The main reasons for this high mortality rate are diagnosis of OC in advanced stages in most patients and spread to distant organs via lymph node metastasis. Many studies have shown that a small population of cells within the tumor plays vital roles in the initiation, progression, and metastasis of the tumor, resistance to chemotherapeutic agents, and recurrence. These cells, identified as cancer stem cells (CSCs), are the main reasons for the failure of current treatment modalities. Deregulated expressions of microRNAs are closely related to tumor prognosis, metastasis and drug resistance. In addition, microRNAs play important roles in regulating the functions of CSCs. Until now, the roles of microRNAs in the acquisition and maintenance of OC stemness have not been elucidated in detail yet. Here in this review, we summarized significant findings and the latest literature to better understand the involvement of CSCs in association with dysregulated microRNAs in oral carcinogenesis. Possible roles of these microRNAs in acquisition and maintenance of CSCs features during OC pathogenesis were summarized., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Prostate cancer (PCa) is one of the most common types of cancer in men. In several recent studies, chromosomal deletions in the q arm of chromosome 2, where ING5 resides within, have been identified in various cancer types including PCa. In this study, we investigate the role of ING5 as a tumor suppressor in PCa. We examined the expression level of ING5 in tissue samples and cell lines using quantitative real-time polymerase chain reaction and western blot analysis. We tested the in vitro tumor suppressor potential of ING5 in PC3 and LNCaP cells stably overexpressing it using cell viability, colony formation, migration, invasion, and apoptosis assays. We then investigated the effects of ING5 on the Akt and p53 signaling using western blot analysis. We show that ING5 is significantly downregulated in PCa tumor tissue samples and cell lines compared with the corresponding controls. In vitro assays demonstrate that ING5 effectively suppresses proliferative, clonogenic, migratory, and invasive potential and induce apoptosis in PCa cells. ING5 may potentially exert its anti-tumor potential by inhibiting AKT and inducing p53 signaling pathways. Our findings demonstrate that ING5 possesses tumor suppressor roles in vitro, pointing its importance during the prostatic carcinogenesis processes., (© 2019 International Federation for Cell Biology.)