scholarly journals miR-375 Suppresses IGF1R Expression and Contributes to Inhibition of Cell Progression in Laryngeal Squamous Cell Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Luo ◽  
Jianhui Wu ◽  
Zenghong Li ◽  
Hao Qin ◽  
Bin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Suppressive Effect ◽  
In Vitro Assays ◽  
Luciferase Reporter

MicroRNAs (miRNAs) are small noncoding RNA molecules which are involved in tumorigenesis and development. To investigate their role in primary laryngeal squamous cell carcinoma (LSCC), miRNA GeneChips were used to screen the differentially expressed miRNA, and then validated by real-time quantitative PCR in LSCC samples, we found that miR-375 was frequently downregulated in primary LSCC tissues. The tumor-suppressive effect of miR-375 was determined by in vitro assays; through gain-of-function studies we demonstrated that miR-375 can inhibit LSCC cell (SNU-48 and SNU-899) proliferation, motility, and invasion, and promote their apoptosis. In addition, bioinformatics tools TargetScan, PicTar, and Miranda were used to investigate the potential target of miR-375; bioinformatics analysis and dual-luciferase reporter assay indicated that IGF1R was a novel direct target of miR-375. Ectopic transfection of miR-375 led to a significant reduction in IGF1R and its downstream signaling molecule AKT at both the mRNA and protein levels in LSCC cells. Our results suggested that downregulation of miR-375 is one of the molecular mechanisms for the development and progression of LSCC by directly targeting IGF1R and affecting its downstream AKT signaling pathways. Furthermore, miR-375 and IGF1R may serve as a novel therapeutic target for LSCC.

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.

scholarly journals The molecular mechanisms of the long noncoding RNA SBF2-AS1 in regulating the proliferation of oesophageal squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjuan Zha ◽  
Xiaomin Li ◽  
Xiaowei Tie ◽  
Yao Xing ◽  
Hao Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Histological Grade ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Lymphnode Metastasis

AbstractThe long noncoding RNASBF2-AS1 can promote the occurrence and development of many kinds of tumours, but its role in oesophageal squamous cell carcinoma (ESCC) is unknown. We found that SBF2-AS1 was up-regulated in ESCC, and its expression was positively correlated with tumor size (P = 0.0001), but was not related to gender, age, TNM stage, histological grade, and lymphnode metastasis (P > 0.05). It was further found that the higher the expression of SBF2-AS1, the lower the survival rate. COX multivariate analysis showed that the expression of SBF2-AS1 was an independent prognostic factor. Functional experiments show that inhibition of SBF2-AS1 can inhibit the proliferation of ESCC through in vivo and in vitro, and overexpression of SBF2-AS1 can promote the proliferation of ESCC and inhibit its apoptosis. In mechanism, SBF2-AS1/miR-338-3P, miR-362-3P/E2F1 axis are involved in the regulation of ESCC growth. In general, SBF2-AS1 may be used as ceRNA to combine with miR-338-3P and miR-362-3P to up-regulate the expression ofE2F1, and ultimately play a role in promoting cancer. It may be used as a therapeutic target and a biomarker for prognosis.

scholarly journals LncRNA GHET1 Promotes Esophageal Squamous Cell Carcinoma Cells Proliferation and Invasion via Induction of EMT

2017 ◽  
Vol 32 (4) ◽  
pp. 403-408 ◽  
Author(s):  
Hongfen Liu ◽  
Qiang Zhen ◽  
Yakun Fan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Advanced Tumor

Background Recent studies have shown that long noncoding RNA (IncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) was involved in the progression of tumors. However, the role of GHET1 in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods The expression of IncRNA GHET1 was examined in 55 paired ESCC tissues and adjacent nontumor tissues. Molecular and cellular techniques were used to explore the role of GHET1 on ESCC cells. Results Our data showed that GHET1 expression was significantly increased in ESCC tissues and cell lines. High GHET1 expression in ESCC tissues was significantly associated with poor differentiation, advanced tumor nodes metastasis stage, and lymph node metastasis. GHET1 showed high sensitivity and specificity for diagnosing ESCC. Our data from in vitro assays showed that GHET1 inhibition suppressed ESCC cells proliferation, migration, and invasion, and induced cells apoptosis. Furthermore, western blot showed that GHET1 inhibition significantly decreased the expression of vimentin and N-cadherin while it increased the expression of E-cadherin. Conclusions Our study indicates that GHET1 acts as an oncogene in ESCC and may represent a novel therapeutic target for the treatment of ESCC patients.

scholarly journals DIAPH1 Is Upregulated and Inhibits Cell Apoptosis through ATR/p53/Caspase-3 Signaling Pathway in Laryngeal Squamous Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jiechao Yang ◽  
Liang Zhou ◽  
Yanping Zhang ◽  
Juan Zheng ◽  
Jian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Poor Overall Survival

Cancer bioinformatics has been used to screen possible key cancer genes and pathways. Here, through bioinformatics analysis, we found that high expression of diaphanous related formin 1 (DIAPH1) was associated with poor overall survival in head and neck squamous cell carcinoma and laryngeal squamous cell carcinoma (LSCC). The effect of DIAPH1 in LSCC has not been previously investigated. Therefore, we evaluated the expression, function, and molecular mechanisms of DIAPH1 in LSCC. Immunohistochemistry and western blot analysis confirmed the significant upregulation of DIAPH1 in LSCC. We used DIAPH1 RNA interference to construct two DIAPH1-knockdown LSCC cell lines, AMC-HN-8 and FD-LSC-1, and validated the knockdown efficiency. Flow cytometry data showed that DIAPH1 inhibited apoptosis. Further, western blot analysis revealed that DIAPH1 knockdown increased the protein levels of ATR, p-p53, Bax, and cleaved caspase-3, -8, and -9. Thus, DIAPH1 is upregulated in LSCC and may act as an oncogene by inhibiting apoptosis through the ATR/p53/caspase-3 pathway in LSCC cells.

scholarly journals SHISA3Promoter Methylation Is a Potential Diagnostic and Prognostic Biomarker for Laryngeal Squamous Cell Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhisen Shen ◽  
Chongchang Zhou ◽  
Jinyun Li ◽  
Dong Ye ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Promoter Methylation ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Prognostic Biomarker ◽  
Promoter Hypermethylation ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Qrt Pcr

The purpose of this study was to evaluate the contribution ofSHISA3promoter methylation to laryngeal squamous cell carcinoma (LSCC).SHISA3promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of theSHISA3promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase inSHISA3methylation in LSCC tissues compared with corresponding nontumor tissuesP=4.58E-12. The qRT-PCR results show a significant association betweenSHISA3methylation and expression in LSCCP=1.67E-03. In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest thatSHISA3promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rankP= 0.024; HR = 2.71; 95% CI = 1.024–7.177;P= 0.047). The results indicate thatSHISA3promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC.

scholarly journals Long Non-Coding RNA CCAT2 Promotes the Development of Esophageal Squamous Cell Carcinoma by Inhibiting miR-200b to Upregulate the IGF2BP2/TK1 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaodan Wu ◽  
Yihui Fan ◽  
Yupeng Liu ◽  
Biao Shen ◽  
Haimin Lu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Non Coding Rna

Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.

scholarly journals The Long Noncoding RNA TUG1 Promotes Laryngeal Cancer Proliferation and Migration

2018 ◽  
Vol 49 (6) ◽  
pp. 2511-2520 ◽  
Author(s):  
Zhonghua Zhang ◽  
Xuehai Wang ◽  
Shengda Cao ◽  
Xiao Han ◽  
Zhanwang Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Cancer Proliferation

Background/Aims: Researchers have shown that long noncoding RNAs are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). However, the role of the long noncoding RNA taurine-upregulated gene 1 (TUG1) in the pathogenesis of LSCC remains unclear, although it is recognized as an oncogenic regulator for several types of squamous cell carcinoma. Methods: qRT-PCR was performed to measure the expression of TUG1 in LSCC tissues and cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was used to measure the effect of TUG1 on cell proliferation. Transwell assay and flow cytometry were employed to determine the effect of TUG1 on cell migration and invasion. Western-blot were performed to explore the relation of TUG1 and p53 mRNA. Results: Higher TUG1 expression in LSCC than in paired normal tumor-adjacent tissue specimens (N = 64) was observed using quantitative real-time polymerase chain reaction. Also, high TUG1 expression was positively associated with advanced T category, worse lymph node metastasis and late clinical stage. Furthermore, in vitro experiments demonstrated that silencing of TUG1 markedly inhibited proliferation, cell-cycle progression, migration, and invasion of LSCC cells, whereas depletion of TUG1 led to increased apoptosis. Conclusion: These findings demonstrated that upregulated TUG1 expression exerted oncogenic effects by promoting proliferation, migration, and invasion, and inhibiting apoptosis in LSCC cells.

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

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