scholarly journals CircPTK2 (hsa_circ_0003221) Contributes to Laryngeal Squamous Cell Carcinoma by the miR-1278/YAP1 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Zhendong Yang ◽  
Jianping Jin ◽  
Tao Chang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Laryngeal Cancer ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Common Type ◽  
Cell Counting ◽  
Circular Rnas ◽  
Squamous Differentiation

Laryngeal cancer accounts for 20% of all head and neck malignancies. Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer and is characterized by squamous differentiation, a high mortality rate, and poor prognosis. Accumulating studies have indicated that circular RNAs (circRNAs) are critical regulators in many cancers. CircPTK2 exerts an important regulatory role in several cancers. In this study, we aimed to elucidate the function of circPTK2 (hsa_circ_0003221) in LSCC. Through a series of investigations, we discovered that circPTK2 was significantly upregulated in LSCC tissues cells. Functionally, cell counting kit-8 (CCK-8) and flow cytometry analyses revealed that knockdown of circPTK2 suppressed LSCC cell viability and the cell cycle while promoting cell apoptosis. Notably, silencing circPTK2 inhibited tumor growth in vivo. Mechanistically, circPTK2 functioned as a molecular sponge of miR-1278 to upregulate YAP1 expression in LSCC cells. Moreover, YAP1 knockdown inhibited malignant phenotypes of LSCC cells. The rescue experiments showed that YAP1 overexpression reversed the effects of circPTK2 on LSCC cells. Therefore, we concluded that circPTK2 facilitates LSCC progression through the miR-1278/YAP1 axis.

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 LncRNA XIST promotes the progression of laryngeal squamous cell carcinoma via sponging miR-125b-5p to modulate TRIB2

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Chunxiu Liu ◽  
Zhenjun Lu ◽  
Hui Liu ◽  
Shenfa Zhuang ◽  
Ping Guo
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Lncrna Xist

Abstract Objective: X inactivate-specific transcript (XIST) is an attractive long noncoding RNA (lncRNA) functioning as an indicator of various human tumors, including laryngeal squamous cell carcinoma (LSCC). The present study was conducted to explore a novel regulatory network of lncRNA XIST in LSCC cells. Materials and methods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression levels of XIST, miR-125b-5p and TRIB2 in LSCC cells and tissues. Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and Transwell assays, separately. The relationship among XIST, miR-125b-5p and tribbles homolog 2 (TRIB2) was predicted by starBase v2.0 or TargetScan and confirmed by Dual-luciferase reporter assay. The TRIB2 protein expression was quantified by Western blot assay. Murine xenograft model was utilized to validate the role of XIST in vivo. Results: XIST was notably up-regulated in LSCC tissues and cells, and the high level of XIST was associated with the low survival rate of LSCC patients. XIST knockdown markedly repressed cell proliferation, migration and invasion and promoted the apoptosis of LSCC cells and the effects were antagonized by loss of miR-125b-5p. MiR-125b-5p was a target of XIST in LSCC cells, and it could bind to TRIB2 as well. Moreover, XIST-loss-induced down-regulation of TRIB2 could be significantly reversed by miR-125b-5p knockdown. XIST promoted the growth of LSCC tumor in vivo. Conclusion: LncRNA XIST promoted the malignance of LSCC cells partly through competitively binding to miR-125b-5p, which in turn increased TRIB2 expression.

Corilagin Inhibits Esophageal Squamous Cell Carcinoma by Inducing DNA Damage and Down-Regulation of RNF8

2019 ◽  
Vol 19 (8) ◽  
pp. 1021-1028 ◽  
Author(s):  
Fanghua Qiu ◽  
Lifang Liu ◽  
Yu Lin ◽  
Zetian Yang ◽  
Feng Qiu
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Apoptosis ◽  
Cell Counting ◽  
Antitumor Effects

Background:Esophageal squamous cell carcinoma (ESCC), the most prevalent histologic subtype of esophageal cancer, is an aggressive malignancy with poor prognosis and a high incidence in the East. Corilagin, an active component present in Phyllanthus niruri L., has been shown to suppress tumor growth in various cancers. However, the effects of corilagin on ESCC and the mechanisms for its tumor suppressive function remain unknown.Methods:Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assays. Annexin V/PI double-staining was performed to assess cell apoptosis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. A xenograft mice model was used to assess the in vivo antitumor effects of corilagin alone or in combination with cisplatin.Results:We for the first time showed that corilagin was effectively able to inhibit ESCC cell proliferation and induce cell apoptosis. Additionally, our results validated its antitumor effects in vivo using a xenograft mouse model. Mechanistically, we found that corilagin caused significant DNA damage in ESCC cells. We found that corilagin could significantly attenuate the expression of the E3 ubiquitin ligase RING finger protein 8 (RNF8) through ubiquitin-proteasome pathway, leading to the inability of DNA damage repair response and eventually causing cell apoptosis. Furthermore, we also showed that corilagin substantially enhanced the antitumor effects of chemotherapy drug cisplatin both in vitro and in vivo.Conclusion:Our results not only provided novel and previously unrecognized evidences for corilagin-induced tumor suppression through inducing DNA damage and targeting RNF8 in ESCC, but also highlighted that corilagin might serve as an adjunctive treatment to conventional chemotherapeutic drugs in ESCC patients.

scholarly journals circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Gao ◽  
Huina Guo ◽  
Min Niu ◽  
Xiwang Zheng ◽  
Yuliang Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Mtor Pathway ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Autophagic Flux ◽  
In Vivo Models ◽  
Potential Biomarker

Abstract Background Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear. Methods The autophagy-suppressive circRNA circPARD3 was identified via RNA sequencing of 107 LSCC tissues and paired adjacent normal mucosal (ANM) tissues and high-content screening. RT-PCR, Sanger sequencing, qPCR and fluorescence in situ hybridization were performed to detect circPARD3 expression and subcellular localization. Biological functions of circPARD3 were assessed by proliferation, migration, invasion, autophagic flux, and chemoresistance assays using in vitro and in vivo models. The mechanism of circPARD3 was investigated by RNA immunoprecipitation, RNA pulldown, luciferase reporter assays, western blotting and immunohistochemical staining. Results Autophagy was inhibited in LSCC, and circPARD3 was upregulated in the LSCC tissues (n = 100, p < 0.001). High circPARD3 level was associated with advanced T stages (p < 0.05), N stages (p = 0.001), clinical stages (p < 0.001), poor differentiation degree (p = 0.025), and poor prognosis (p = 0.002) of LSCC patients (n = 100). Functionally, circPARD3 inhibited autophagy and promoted LSCC cell proliferation, migration, invasion and chemoresistance. We further revealed that activation of the PRKCI-Akt-mTOR pathway through sponging miR-145-5p was the main mechanism of circPARD3 inhibited autophagy, promoting LSCC progression and chemoresistance. Conclusion Our study reveals that the novel autophagy-suppressive circPARD3 promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagy regulation and potential biomarker and target for LSCC treatment. Graphical abstract

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 Downregulation of miR-29c-3p is associated with a poor prognosis in patients with laryngeal squamous cell carcinoma

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Ruihua Fang ◽  
Yongjin Huang ◽  
Jinghua Xie ◽  
Jianzhong Zhang ◽  
Xiaobin Ji
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Laryngeal Cancer ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Hazard Analysis ◽  
Clinicopathological Characteristics ◽  
Rank Test

Abstract Background Laryngeal squamous cell carcinoma (LSCC) is considered to be a common malignancy of the head and neck with poor prognosis for its late diagnosis, metastasis and recurrence. Growing evidence demonstrates that the dysregulation of miR-29c-3p (microRNA-29c-3p) plays an important role in various tumor processes. Our study investigates the expression of miR-29c-3p in LSCC and analyzes the correlation of its dysregulation with clinicopathologic parameters and prognosis. Methods The expression of hsa-miR-29c-3p in LSCC tissues and the adjacent normal laryngeal tissues was detected in 96 LSCC formalin-fixed paraffin-embedded tissues by quantitative real-time PCR (qRT-PCR). The SPSS statistical software package (17.0) was used to analyze the associations between miR-29c-3p expressions and various clinicopathological characteristics. The overall survival (OS) was analyzed by the Kaplan-Meier method and log-rank test, and we analyzed the independent factor of prognosis by Cox proportional hazard analysis. Results A downregulation of miR-29c-3p expression in LSCC was significantly correlated with smoking index, tumor size, tumor site, differentiation, T classification, TNM stage, and lymph node metastasis (P < 0.05), but there was no correlation with age and alcohol consumption (P > 0.05). In the multivariate survival analysis, low miR-29c-3p expression was associated with shorter overall survival (P < 0.05). Furthermore, miR-29c expression was an independent prognostic factor for laryngeal cancer patients. Conclusions MiR-29c-3p has different expression levels at different stages of tumor progression, suggesting that miR-29c-3p may be a promising biomarker for evaluating the progression of LSCC and the prognosis of patients with LSCC. MiR-29c-3p can also be a novel molecular target for anti-laryngeal cancer therapy.

scholarly journals Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced by andrographolide via upregulation of phospho-p53 in vitro and in vivo

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770533 ◽  
Author(s):  
Songjie Chen ◽  
Hui Hu ◽  
Shushu Miao ◽  
Jiayong Zheng ◽  
Zhijian Xie ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Regression ◽  
Cell Counting ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Ki 67

Oral squamous cell carcinoma is one of the most common neoplasm in the world. Despite the improvements in diagnosis and treatment, the outcome is still poor now. Thus, the development of novel therapeuticapproaches is needed. The aim of this study is to assess the synergistic anti-tumor effect of andrographolide with cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and western blotting on CAL-27 cells treated with andrographolide, DDP or the combination in vitro. In vivo, we also treated CAL-27 xenografts with andrographolide or the combination, and performed terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis of Ki-67. The results showed the combination of andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition, the synergistic anti-tumor effect of andrographolide with synergistic was due to an enhanced apoptosis. Moreover, the combination therapy upregulated the expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our data indicate that the combination treatment of andrographolide and DDP results in synergistic anti-tumor growth activity against oral squamous cell carcinoma CAL-27 in vitro and in vivo. These results demonstrated that combination of andrographolide with DDP was likely to represent a potential therapeutic strategy for oral squamous cell carcinoma.

scholarly journals Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jian-Xing Wang ◽  
Xin-Ju Jia ◽  
Yan Liu ◽  
Jin-Hui Dong ◽  
Xiu-Min Ren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Laryngeal Squamous Cell Carcinoma

Abstract Background Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown. Methods qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo. Results In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3′-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway. Conclusions In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment.

scholarly journals CircRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/IGF-1R axis

2019 ◽  
Vol 133 (9) ◽  
pp. 1053-1066 ◽  
Author(s):  
Linli Tian ◽  
Jing Cao ◽  
Hui Jiao ◽  
Jiarui Zhang ◽  
Xiuxia Ren ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Central Component ◽  
Reporter System

Abstract Background: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA–microRNA (miRNA)–mRNA interaction. Methods: We investigated the expression of circRNAs in three paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs and 414 down-regulated circRNAs. We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. Results: circRASSF2 was found to be significantly up-regulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration in vitro, which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth in vivo. Importantly, we demonstrated that circRASSF2 was up-regulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression. Conclusion: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis.

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