scholarly journals LINC00319 promotes cancer stem cell-like properties in laryngeal squamous cell carcinoma via E2F1-mediated upregulation of HMGB3

2021 ◽  
Author(s):  
Linlin Yuan ◽  
Xiufen Tian ◽  
Yanfei Zhang ◽  
Xinhui Huang ◽  
Qing Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Noncoding Rnas ◽  
High Mobility ◽  
Self Renewal

AbstractLaryngeal squamous cell carcinoma (LSCC) is one of the most common subtypes of head and neck malignancies worldwide. Long intervening/intergenic noncoding RNAs (LINCRNAs) have been recently implicated in various biological processes that take place in the setting of laryngeal cancer, but the regulatory role of LINC00319 in LSCC remains largely unknown. The current study aimed to elucidate the regulatory effect of LINC00319 on the development and progression of LSCC via high-mobility group box 3 (HMGB3). Microarray-based analysis was initially conducted to identify differentially expressed long noncoding RNAs, after which the expression of LINC00319 and HMGB3 in LSCC tissues and cells was determined accordingly. CD133+CD144+ TU177 cells were subsequently isolated and transfected with LINC00319 overexpression vector (oe-LINC00319), short hairpin RNA (sh)-LINC00319, sh-HMGB3, sh-E2F transcription factor 1 (E2F1), and oe-E2F1, as well as their corresponding controls. The proliferative, invasion, self-renewal, and tumorigenic abilities of CD133+CD144+ TU177 cells were then evaluated. Our in vitro findings were further confirmed following subcutaneous injection of cells expressing the corresponding plasmids into nude mice. LINC00319 and HMGB3 expressions were elevated in LSCC cells and tissues. LINC00319 increased HMGB3 expression by recruiting E2F1. Furthermore, the stimulatory role of LINC00319 on the proliferation, invasion, self-renewal ability, and tumorigenicity of CD133+CD144+ TU177 cells was achieved by upregulating HMGB3 via recruitment of E2F1. The in vitro findings were also confirmed by in vivo experiments. Taken together, these data show that downregulating LINC00319 in CD133+CD144+ TU177 cells may serve as a potential anticancer regimen by inhibiting the proliferation and invasion of cancer stem cells in LSCC.

scholarly journals Targeting SKA3 suppresses the proliferation and chemoresistance of laryngeal squamous cell carcinoma via impairing PLK1–AKT axis-mediated glycolysis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Wei Gao ◽  
Yuliang Zhang ◽  
Hongjie Luo ◽  
Min Niu ◽  
Xiwang Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Critical Role ◽  
In Vivo Experiments ◽  
Potential Strategy

Abstract Spindle and kinetochore-associated complex subunit 3 (SKA3) is a well-known regulator of chromosome separation and cell division, which plays an important role in cell proliferation. However, the mechanism of SKA3 regulating tumor proliferation via reprogramming metabolism is unknown. Here, SKA3 is identified as an oncogene in laryngeal squamous cell carcinoma (LSCC), and high levels of SKA3 are closely associated with malignant progression and poor prognosis. In vitro and in vivo experiments demonstrate that SKA3 promotes LSCC cell proliferation and chemoresistance through a novel role of reprogramming glycolytic metabolism. Further studies reveal the downstream mechanisms of SKA3, which can bind and stabilize polo-like kinase 1 (PLK1) protein via suppressing ubiquitin-mediated degradation. The accumulation of PLK1 activates AKT and thus upregulates glycolytic enzymes HK2, PFKFB3, and PDK1, resulting in enhancement of glycolysis. Furthermore, our data reveal that phosphorylation at Thr360 of SKA3 is critical for its binding to PLK1 and the increase in glycolysis. Collectively, the novel oncogenic signal axis “SKA3-PLK1-AKT” plays a critical role in the glycolysis of LSCC. SKA3 may serve as a prognostic biomarker and therapeutic target, providing a potential strategy for proliferation inhibition and chemosensitization in tumors, especially for LSCC patients with PLK1 inhibitor resistance.

scholarly journals Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaofeng Qi ◽  
Wengguang Xu ◽  
Junqi Xie ◽  
Yufeng Wang ◽  
Shengwei Han ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Carcinoma Cells ◽  
Oral Cancers ◽  
Underlying Mechanisms

Abstract Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both in vitro and in vivo, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers.

scholarly journals hsa_circ_0023305 Enhances Laryngeal Squamous Cell Carcinoma Progression and Modulates TRPM7 via miR-218-5p Sponging

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yi Zhang ◽  
Kaisai Tian ◽  
Enhui Zhou ◽  
Xiaocheng Xue ◽  
Shiling Yan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Transient Receptor Potential ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Circular Rnas ◽  
Node Metastasis ◽  
Proliferation And Invasion

Recently, circular RNAs have been shown to function as critical regulators of many human cancers. However, the circRNA mechanism in laryngeal squamous cell carcinoma (LSCC) remains elusive. Recent investigations using bioinformatics analysis revealed high expression of hsa_circ_0023305 in LSCC tissues compared to normal tissues. Furthermore, we discovered that hsa_circ_0023305 expression level was positively correlated to tumor/node/metastasis (TNM) stage as well as lymph node metastasis in LSCC. Moreover, higher hsa_circ_0023305 levels were correlated to poorer LSCC patient outcomes. Knockdown of hsa_circ_0023305 significantly inhibited LSCC cell proliferation, invasion, and migration abilities. Our team validated that hsa_circ_0023305 functioned as a miR-218-5p sponge from a mechanistic perspective, targeting the melastatin-related transient receptor potential 7 (TRPM7) in LSCC cells. TRPM7 regulates a nonselective cation channel and promotes cancer proliferation and metastasis. Our data demonstrated that miR-218-5p was downregulated in LSCC and that miR-218-5p upregulation repressed LSCC proliferation and invasion both in vivo and in vitro. Additionally, we found that hsa_circ_0023305-mediated upregulation of TRPM7 inhibited miR-218-5p and contributed to LSCC migration, proliferation, and invasion. In summary, these data propose a new mechanism by which the hsa_circ_0023305/miR-218-5p/TRPM7 network enhances LSCC progression.

Melatonin and oral squamous cell carcinoma: current knowledge and future perspectives

2019 ◽  
Vol 2 (1) ◽  
pp. 94-105
Author(s):  
Omid Reza Tamtaji ◽  
Moein Mobini ◽  
Amir Abbas Atlasi ◽  
Ehsan Dadgostar ◽  
Zatollah Asemi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Current Knowledge ◽  
Apoptotic Pathways ◽  
Tumor Associated Neutrophils

On the basis of worldwide ranking, oral cancer is the eighth most prevalent cancer. Oral squamous cell carcinoma is a cancer that occurs following dysplasia of the mucosa of the oral cavity and oropharynx. There are different inflammatory pathways involved in the pathophysiology of oral squamous cell carcinoma. Melatonin (N-acetyl-5-methoxytryptamine), a well documented anticancer agent, exhibits numerous functions including induction of apoptotic pathways and controlling of oxidative stress. In the in vivo and in vitro studies the results have demonstrated that melatonin supplementation is an appropriate therapeutic approach for oral squamous cell carcinoma. Melatonin might inhibit cancer cells through the regulation of molecular pathways including AKT/mTOR pathway, ERK/AKT signaling, LSD1 expression and tumor-associated neutrophils releasing. Limited clinical studies; however, have evaluated the role of melatonin in oral squamous cell carcinoma. This review summarizes current knowledge and evidence regarding the effects of melatonin on oral squamous cell carcinoma and the mechanisms involved.  

scholarly journals Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway

2019 ◽  
Vol 244 (13) ◽  
pp. 1070-1080 ◽  
Author(s):  
Hao Wu ◽  
Juanjuan Li ◽  
Jianqiu Chen ◽  
Yong Yin ◽  
Peng Da ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Exposure ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Pdx Model

The present study explored the role of LAMP3 and related molecular mechanisms in the efficacy of radiation exposure in laryngeal squamous cell carcinoma (LSCC). A lentivirus vector containing the LAMP3 gene was transfected into HEp-2 cells to construct siRNA-LAMP3 and complementation (siLAMP3+LAMP3) groups. Treatment with 4 Gy or 8 Gy radiation was administered to evaluate the role of LAMP3 in radiation therapy. Apoptosis was detected by Annexin V/propidium iodide double staining. Cell migration and invasion were measured in vitro using Transwell and Matrigel assays. Downstream genes regulated by LAMP3 were analyzed using RNA sequencing. Furthermore, a patient-derived xenograft (PDX) model of LSCC was established to verify the efficacy of radiation exposure and the associated signaling pathways downstream of LAMP3. The efficacy of radiation showed that cell proliferation was significantly inhibited by siRNA-LAMP3 knockdown. Increased apoptosis was also observed. Notably, the inhibitory effect was attenuated and apoptosis rates were decreased after LAMP3 complementation. In vitro cellular assays showed that migration and invasion were significantly suppressed by siRNA-LAMP3 knockdown and increased after LAMP3 complementation. Analysis of the efficacy of radiation exposure in the PDX model showed that LAMP3-specific knockdown inhibited tumor growth and that tumor growth was further reduced by the combined radiotherapy treatment. According to transcriptome analysis, the extracellular matrix-receptor interaction pathway is regulated by LAMP3, and further analysis revealed significant differences in key-associated molecules, including laminin subunit gamma-2 (LAMC2) and tenascin-C (TNC). Validation of the in vivo PDX model using qPCR and Western blot analyses supported the abovementioned results. The present findings suggest that reduced LAMP3 expression enhances the efficacy of radiation exposure in LSCC by regulating the LAMP3/LAMC2/TNC signaling pathway. Impact statement It is important to establish effective early diagnostic indicators and reliable treatment strategies for laryngeal squamous cell carcinoma (LSCC). We previously found that expression of LAMP3 was significantly higher in cancerous tissues compared to adjacent normal surgical margin tissues. The present study explored the role of LAMP3 and the related molecular mechanisms in the efficacy of radiation exposure in LSCC. In vitro Transwell and Matrigel assays were performed, and a patient-derived xenograft (PDX) model of LSCC was established. Associated signaling pathways downstream of LAMP3 were analyzed using RNA sequencing. Signaling pathways regulated by LAMP3 were clearly identified by combining the PDX model with transcriptome analysis. Reduced LAMP3 expression enhanced the efficacy of radiation exposure in LSCC. Thus, by utilizing this molecule as a marker, specific groups of patients may be screened for targeted therapy in the future.

scholarly journals TGIF2-Induced HMGB3 Promotes Esophageal Squamous Cell Carcinoma Progression Through TGFβ Signaling

2021 ◽  
Author(s):  
Liaoran Niu ◽  
Wanli Yang ◽  
Wei Zhou ◽  
Lili Duan ◽  
Xiaoqian Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
High Mobility ◽  
Prognostic Indicators ◽  
Proliferation And Metastasis

Abstract Background: Proliferation and metastasis are the major malignant phenotypes of esophageal squamous cell carcinoma (ESCC) and the main causes for poor survival in patients with ESCC. Nevertheless, the underlying mechanisms of ESCC proliferation and metastasis remains unclear. The high mobility group box protein family 3 (HMGB3) is one of the HMGB family members. It is critically involved in the occurrence and development of various carcinomas. However, the knowledge of HMGB3 in ESCC remains limited. In this study, we elucidated the role of HMGB3 in ESCC proliferation and metastasis, and the concrete mechanism. Methods: Expression level of HMGB3 and TGF-β interacting factor 2 (TGIF2) in ESCC cell lines and tissues was quantified by qRT-PCR, Western Blot, and immunohistochemistry. In vitro and in vivo assays revealed the functions of TGIF2 and HMGB3 in ESCC. RNA-seq was performed to search for the downstream signaling of HMGB3. ChIP assay and were performed to explore the relationship of HMGB3 and TGIF2. HMGB3-interacting protein was validated by immunoprecipitation.Results: Higher expression of TGIF2 and HMGB3 was observed in ESCC cell lines and tissues and was associated with worse prognosis of ESCC patients. TGIF2 and HMGB3 upregulation could promote ESCC proliferation and metastasis, and vice versa. TGIF2 and HMGB3 upregulation can activate Smad-dependent TGF-β signaling. TGIF2 can transcriptionally regulate HMGB3, and its TGF-β inducing capability and oncogenic role are at least partly HMGB3-dependent. Additionally, TLR3 was identified as a client protein of HMGB3, and their combination might be the reason of TGF-β activation. Conclusions: Collectively, HMGB3-dependent TGIF2 overexpression activates TGF-β signaling and promotes the proliferation and metastasis of ESCC via TLR3 regulation. These findings revealed that TGIF2 and HMGB3 could be prognostic indicators of ESCC and targeting TGIF2/HMGB3/TLR3 axis might improve the OS of ESCC patients.

scholarly journals OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Xiu-Ping Tu ◽  
Hao Li ◽  
Liang-Si Chen ◽  
Xiao-Ning Luo ◽  
Zhong-Ming Lu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Direct Target

Abstract Background Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism.Methods The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. Results OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo. Conclusions Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.

scholarly journals OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Xiu-Ping Tu ◽  
Hao Li ◽  
Liang-Si Chen ◽  
Xiao-Ning Luo ◽  
Zhong-Ming Lu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Direct Target

Abstract Background Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism. Methods The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. Results OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo . Conclusions Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.

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