H19/miR‐107/HMGB1 axis sensitizes laryngeal squamous cell carcinoma to cisplatin by suppressing autophagy in vitro and in vivo

2020 ◽  
Author(s):  
Liwei Chen ◽  
Zhijian Xu ◽  
Jiandong Zhao ◽  
Xingyou Zhai ◽  
Jianhui Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma

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 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.

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 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.

scholarly journals CD47 is a Potential Target for the Treatment of Laryngeal Squamous Cell Carcinoma

2016 ◽  
Vol 40 (1-2) ◽  
pp. 126-136 ◽  
Author(s):  
ChunPing Yang ◽  
ShuFeng Gao ◽  
HaiZhen Zhang ◽  
Lian Xu ◽  
JianGuo Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Protein Expressions

Background/Aims: This study aims to investigate the effect of CD47 on the development of laryngeal squamous cell carcinoma (LSCC) and the therapeutic potential of monoclonal antibody against CD47 and its ligand SIRPα in the treatment of LSCC. Methods: We firstly detected the expressions of CD47 mRNA and protein in LSCC and para-carcinoma tissues, introduced the most efficient CD47siRNA sequence into LSCC cells by lentiviral transfection and employed three monoclonal antibodies to evaluate their anti-LSCC effects in vitro and in vivo. Results: We observed that the mRNA and protein expressions of CD47 in LSCC tissue had significant increase in LSCC tissues compared with those in para-carcinoma tissue (p < 0.05). After the treatments of three monoclonal antibodies, i.e. anti-SIRPα, anti-CD47 BRIC126, anti-CD47 B6H12.2, in rats transfected with Hep-2 cell, it has been showed that the mRNA and protein expressions of CD47 in LSCC tissue decreased, macrophage efficiency was promoted when anti-SIRPα and/or CD47siRNA were used, the amounts, viabilities and expressions of CD47 protein of tumor cell were significantly inhibited. Additionally, combined use of CD47siRNA and anti-SIRPα seemed more efficient than solo use of CD47siRNA/anti-SIRPα. Conclusion: The results suggested a critical role of CD47 in LSCC development and the promising treatment of antiCD47/SIRPα and/or CD47siRNA in LSCC.

scholarly journals Molecular mechanism of targeted inhibition of HMGA2 via miRNAlet-7a in proliferation and metastasis of laryngeal squamous cell carcinoma

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Li-Juan Ma ◽  
Jun Wu ◽  
En Zhou ◽  
Juan Yin ◽  
Xu-Ping Xiao
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cell Model ◽  
Xenograft Model ◽  
Luciferase Assay

Abstract MiRNAlet-7a is associated with the tumorigenesis of laryngeal squamous cell carcinoma (LSCC). Our study was designed to infer whether let-7a targets high-mobility AT-hook 2 (HMGA2) and suppresses laryngeal carcinoma cell proliferation, invasion, and migration. The expression levels of let-7a and HMGA2 were measured in 30 LSCC clinical specimens by qRT-PCR and their correlation was analyzed. Cell model and mice xenograft model with or without let-7a overexpression were constructed to evaluate the effects of let-7a on LSCC. Moreover, luciferase assay was performed to reveal the interaction between let-7a and HMGA2, which was further verified in xenograft. Let-7a was significantly down-regulated and HMGA2 was up-regulated in LSCC tissues compared with normal tissues (P&lt;0.05), both of which were significantly correlated with TNM stage and lymph node metastases of LSCC patients (P&lt;0.05). We also observed a negative correlation between let-7a and HMGA2 expression in LSCC samples (r = −0.642, P&lt;0.05). In vitro and in vivo experiments demonstrated that let-7a overexpression could inhibit cell proliferation and tumor growth of LSCC and simultaneously down-regulate the expression of HMGA2. Moreover, the regulation of HMGA2 by let-7a was also proved by luciferase assay. Our results revealed that let-7a promotes development and progression of LSCC through inhibiting the expression of HMGA2. Therefore, let-7a may thus be a potential diagnostic biomarker and therapeutic target for treating 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 important roles in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aim to explore the roles of OTX1 in LSCC and 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 computer algorithm and confirmed experimentally.Results OTX1 was highly expressed in 70.7% (70/99) of LSCC patient tissues. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in LSCC patients was correlated with poor prognosis. Knockdown of OTX1 inhibits proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibits tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhances 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, OTX1as 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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