miR-206 Inhibits Laryngeal Carcinoma Cell Multiplication, Migration, and Invasion

Laryngeal carcinoma (LC) is one of the common human cancer types. MicroRNAs (miRNAs) were reported to be the essential regulators in cancer diagnosis, treatment, and prognosis. It was reported that miR-206 expression was reduced in various neoplastic diseases. However, the role and functional mechanism of miR-206 in LC progression remain unclear. In this research, miR-206 was found to be associated with tumor-node-metastasis (TNM) staging. In addition, the area under the curve (AUC) of miR-206 was 0.902 for diagnosis of LC and 0.854 for differential diagnosis of stage I-II and stage III-IV patients. Low expression of miR-206 was associated with poor prognosis of LC patients. miR-206 expression was an independent factor affecting the prognosis of LC patients, as revealed by the Cox regression analysis. In vitro experiments demonstrated that miR-206 overexpression reduced cell multiplication, invasion, and migration and increased cell apoptosis in LC cells. Moreover, SOX9 was a target of miR-206, and miR-206 negatively regulated SOX9 expression. Collectively, miR-206 might be a promising biomarker with diagnostic and prognostic value for LC, and the miR-206/SOX9 axis might be a candidate target for LC therapy.

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Expression of Long Non-Coding RNA PANDAR and its Prognostic Value in Colorectal Cancer Patients

The International Journal of Biological Markers ◽

10.5301/jbm.5000249 ◽

2017 ◽

Vol 32 (2) ◽

pp. 218-223 ◽

Cited By ~ 13

Author(s):

Xiangke Li ◽

Feng Wang ◽

Yan Sun ◽

Qingxia Fan ◽

Guangfei Cui

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Human Cancer ◽

Expression Level ◽

Migration And Invasion ◽

Cox Regression Analysis ◽

Relative Expression Level ◽

Kaplan Meier ◽

Colorectal Cancer Patients

Background Long noncoding RNAs (lncRNAs) are emerging as key molecules in human cancer. In the present study, we explored the role of the lncRNA PANDAR in colorectal cancer (CRC). Methods The relative expression level of lncRNA PANDAR in CRC tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The associations between PANDAR expression and clinicopathological features of CRC patients were further analyzed. Kaplan-Meier survival analysis was performed to evaluate the value of PANDAR in the prognosis of CRC patients. Furthermore, the biological function of PANDAR on CRC cell growth, apoptosis and mobility was investigated through MTT, flow cytometry, transwell migration and invasion assays in vitro. Results The expression level of PANDAR was higher in CRC tissues and cells compared with adjacent nontumor tissues and normal colonic cell line NCM460. PANDAR expression was significantly correlated with local invasion, lymph node metastasis and TNM stage. Kaplan-Meier analysis showed that patients with high PANDAR expression had poorer overall survival than patients with low PANDAR expression. Multivariate Cox regression analysis indicated that PANDAR might be an independent prognostic factor for CRC patients. Furthermore, PANDAR knockdown significantly inhibited cell proliferation, cycle progression, migration and invasion of CRC in vitro. Conclusions Our results suggest that high expression of PANDAR was involved in CRC progression and could act as an independent biomarker for prognosis of CRC patients.

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Serum exosomal miR-4787-3p as potential lymph node metastasis and prognostic marker in esophageal squamous cell carcinoma.

10.21203/rs.3.rs-317660/v1 ◽

2021 ◽

Author(s):

Shuang Liu ◽

Zheng Lin ◽

Jianwen Wang ◽

Zerong Zheng ◽

Wenqing Rao ◽

...

Keyword(s):

Regression Analysis ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cox Regression ◽

High Serum ◽

Migration And Invasion ◽

Cox Regression Analysis ◽

Mirna Array ◽

Node Metastasis

Abstract Background: To explore the miR-4787-3p expression levels in the serum exosome and tissue and its role in lymph node metastasis and prognosis in ESCC. Methods: The miRNA array was conducted to detect the ESCC serum exosomal miRNAs expression. A receiver operating characteristic (ROC) curve was constructed to determine the predictive ESCC with lymph node metastasis efficacy of serum exosomal miR-4784-3p. The Cox regression analysis was preformed to explore prognostic factors for ESCC. Transwell assay and CCK-8 assays were utilized to evaluate cell migration, invasion, and proliferation, respectively. Results: High serum exosomal miR-4787-3p expression was demonstrated in lymph node metastasis group (P =0.011). The serum exosomal miR-4787-3p expression was significantly associated with histologic grade (P = 0.010), and TNM stage (P = 0.033). However, there was no significant relationship between tissue miR-4787-3p expression and clinical characteristics (P >0.05). ROC analyses revealed that the AUCs of serum exosomal miR-4787-3p for lymph node metastasis prediction was 0.787. The Cox regression analysis found that high expression serum exosomal miR-4787-3p were correlated with poor prognoses (for OS, HR=2.68, 95% CI: 1.02~7.04; for DFS, HR = 2.65, 95% CI: 1.05~6.68). Nevertheless, no association between tissue miR-4787-3p expression and ESCC prognosis. In addition, upregulated expression of miR-4787-3p could promote migration and invasion in vitro. Conclusions: Serum exosomal miR-4787-3p can be promising biomarkers for ESCC metastasis and prognosis

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MicroRNA-99b predicts clinical outcome of osteosarcoma and suppresses tumor cell proliferation, migration and invasion

Diagnostic Pathology ◽

10.1186/s13000-019-0889-y ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Xin Shi ◽

Xingfa Guan

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Prognostic Value ◽

Cox Regression ◽

Expression Profiles ◽

Migration And Invasion ◽

Aberrant Expression ◽

Cox Regression Analysis ◽

Normal Tissues

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.

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Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01717-5 ◽

2020 ◽

Vol 39 (1) ◽

Cited By ~ 1

Author(s):

Xiaojian Zhu ◽

Fanqin Bu ◽

Ting Tan ◽

Qilin Luo ◽

Jinfeng Zhu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

In Situ Hybridization ◽

Cox Regression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Cox Regression Analysis

Abstract Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo. Results We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

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Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer

10.21203/rs.3.rs-25530/v2 ◽

2020 ◽

Author(s):

xiaojian zhu ◽

Fanqin Bu ◽

Ting Tan ◽

Qilin Luo ◽

Jingfeng Zhu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

In Situ Hybridization ◽

Cox Regression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Cox Regression Analysis

Abstract Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods: An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivio . Results: We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo . Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo . Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions: Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

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MiR-455-3p downregulation facilitates cell proliferation and invasion and predicts poor prognosis of osteosarcoma

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-01967-1 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Xijun Yi ◽

Yafei Wang ◽

Shijie Xu

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Cox Regression ◽

Clinical Stage ◽

Prognostic Indicator ◽

Cell Counting ◽

Migration And Invasion ◽

Cox Regression Analysis ◽

Cox Analysis

Abstract Background Osteosarcoma (OS) is one of the most primary malignant bone tumors, mainly attracting children and young adults. The microRNAs are mentioned to play vital roles in many cancers, including OS. The purpose of this study was to explore the expression and function of miR-455-3p in OS and predict the potential effects in clinical diagnosis and prognosis. Method We conducted quantitative real-time PCR to assess the expression of miR-455-3p in OS tissues and cell lines. The Cell Counting Kit-8 assay, Transwell assay, and flow cytometry were performed to assess the ability of miR-455-3p on cell proliferation, migration, invasion, and apoptosis. Kaplan–Meier curve and Cox regression analysis were used to demonstrate the survival outcome. Results This study revealed that the expression of miR-455-3p was decreased in OS tissues and cell lines. The dysregulation of miR-455-3p was in association with tumor size, distant metastasis, and clinical stage. Patients with high miR-455-3p expression had a satisfying survival rate. Multivariate Cox analysis indicated that miR-455-3p was a promising prognostic indicator. Expression of miR-455-3p could inhibit the proliferation, migration, and invasion, and facilitate apoptosis of OS cells in vitro. Conclusion These results indicated the miR-455-3p was a potential clinical therapeutic target and prognostic biomarker by suppressing the proliferation, migration, and invasion, as well as enhancing cell apoptosis.

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The Novel Role of LINC01235 in Metastasis of Gastric Cancer Cells by Inducing Epithelial-mesenchymal Transition

10.21203/rs.3.rs-50590/v1 ◽

2020 ◽

Author(s):

Cheng Zhang ◽

Yu Liang ◽

Chun-Dong Zhang ◽

Dong-Qiu Dai

Keyword(s):

Gastric Cancer ◽

Cox Regression ◽

Migration And Invasion ◽

Rna Seq ◽

Pcr Assay ◽

Cox Regression Analysis ◽

Qrt Pcr ◽

Overall Survival Analysis

Abstract BackgroundLncRNAs play a vital role in the tumorigenesis of gastric cancer (GC). The present study aims to explore the role of LINC01235 in clinical significance, prognostic prediction and GC metastasis.MethodsWe identified differentially expressed lncRNAs using stomach adenocarcinoma RNA-Seq data from The Cancer Genome Atlas (TCGA). The expression of LINC01235 in GC cell lines and tissues were confirmed by qRT-PCR assay. The overall survival analysis and univariate/ multivariate Cox regression analysis were performed to explore the prognostic value of LINC01235. In vitro assays were utilized to assess the effect of LINC01235 in cell migration and invasion. Western blotting measured the expression of EMT-induced proteins.ResultsThis study determined that LINC01235 expression has a higher fold changes by analyzing TCGA RNA-Seq data. qRT-PCR assay confirmed that LINC01235 is significantly over-expressed in GC cells and tissues. Additionally, the overall survival analysis showed that patients with a higher LINC01235 expression had a poorer prognosis than those with a lower LINC01235 expression. Univariate Cox regression analysis indicated that high LINC01235 expression is positively correlated with poor prognosis. Moreover, LINC01235 was an independent poor prognostic marker for GC in multivariate Cox analysis. In vitro assays suggested that LINC01235 knockdown suppresses GC cell migration and invasion. GSEA revealed that high LINC01235 expression is strongly enriched in EMT pathway. Western blotting results revealed that LINC01235 silencing decreases the expression of EMT-induced proteins.ConclusionLINC01235 could promote GC cell metastasis via EMT and function as a prognostic biomarker.

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KRT18 is correlated with the malignant status and acts as an oncogene in colorectal cancer

Bioscience Reports ◽

10.1042/bsr20190884 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 4

Author(s):

Jingfeng Zhang ◽

Sifeng Hu ◽

Yansen Li

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Clinical Stage ◽

Human Tumor ◽

Migration And Invasion ◽

Epithelial Cell Line ◽

Advanced Clinical Stage ◽

Cox Regression Analysis ◽

Keratin 18

Abstract Keratin 18 (KRT18) has been suggested to be overexpressed in most types of human tumor, but the expression pattern of KRT18 in colorectal cancer (CRC) remained unknown. In our research, KRT18 protein expression was markedly increased in CRC cancer tissues and cell lines compared with adjacent normal colorectal tissues and normal colonic epithelial cell line, respectively. Meanwhile, we observed high KRT18 expression was associated with advanced clinical stage, deep tumor invasion, lymph node metastasis, distant metastasis, poor differentiation and unfavorable prognosis in CRC patients. Multivariate Cox regression analysis showed high expression of KRT18 was an unfavorable independent predictor for overall survival in CRC patients. The in vitro studies indicated down-regulation of KRT18 expression depressed CRC cell viability, migration and invasion. In conclusion, KRT18 serves as an oncogenic role in CRC progression and may be a therapeutic target for promoting CRC patients’ prognosis.

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FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC

Cellular Physiology and Biochemistry ◽

10.1159/000495962 ◽

2018 ◽

Vol 51 (6) ◽

pp. 2716-2731 ◽

Cited By ~ 11

Author(s):

Dan Li ◽

Suyun Fan ◽

Fei Yu ◽

Xuchao Zhu ◽

Yingchun Song ◽

...

Keyword(s):

Proportional Hazards Model ◽

Cox Regression ◽

Disease Free Survival ◽

Cox Proportional Hazards Model ◽

Migration And Invasion ◽

Rank Test ◽

Cox Regression Analysis ◽

Nsclc Patients

Background/Aims: Forkhead box D1 (FOXD1) has a well-established role in early embryonic development and organogenesis and functions as an oncogene in several cancers. However, the clinical significance and biological roles of FOXD1 in non-small cell lung cancer (NSCLC) remain largely unknown. Methods: A total of 264 primary NSCLC tissue samples were collected. The expression levels of FOXD1 in these samples were examined by immunohistochemical staining. The expression of FOXD1 was knocked down by lentiviral shRNA. The relative expression of FOXD1 was determined by qRT-PCR, Western blotting and immunofluorescence image. The functional roles of FOXD1 in NSCLC were demonstrated cell viability CCK-8 assay, colony formation, cell invasion and migration assays, and cell apoptosis assay in vitro. In vivo mouse xenograft and metastasis models were used to assess tumorigenicity and metastatic ability. The Chi-square test was used to assess the correlation between FOXD1 expression and the clinicopathological characteristics. Survival curves were estimated by Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Results: We determined that higher levels of FOXD1 were present in NSCLC tissues, especially in metastatic NSCLC tissues. FOXD1 was also higher in all NSCLC cells compared with normal human bronchial epithelial cells. A higher expression level of FOXD1 was associated with malignant behavior and poor prognosis in NSCLC patients. Knockdown of FOXD1 significantly inhibited proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo, and it increased the apoptosis rates of NSCLC cells. Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in NSCLC. Multivariate Cox regression analysis indicated that FOXD1 was an independent prognostic factor both for overall survival (OS) and disease-free survival (DFS) in NSCLC patients. Conclusion: Our results indicated that FOXD1 might be involved in the development and progression of NSCLC as an oncogene, and thereby might be a potential therapeutic target for NSCLC patients.

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SHCBP1 interacting with EOGT enhanced O-GlcNAcylation of NOTCH1 and promoted the development of pancreatic cancer .

10.21203/rs.3.rs-95104/v1 ◽

2020 ◽

Author(s):

Can Yang ◽

Jianfei Hu ◽

Qian Zhan ◽

Zu-Wei Wang ◽

Ge Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

Developmental Disorders ◽

High Throughput Sequencing ◽

Cox Regression ◽

Sh2 Domain ◽

Migration And Invasion ◽

Cox Regression Analysis ◽

Xenograft Growth

Abstract Background: Pancreatic cancer(PDAC) remains one of the most lethal cancers worldwide, The accumulation of many abnormal epigenetic abnormalities contribute to the fatal prognosis of PDAC,While available studies are still limited. Many studies have confirmed that the Shc SH2-domain binding protein 1(SHCBP1) plays as proto-oncogene in cancers. However, whether SHCBP1 plays a role in pancreatic cancer oncogenesis is still unknown.EGF domain-specific O-linked GlcNActransferase (EOGT) acts as a key participant in the O-GlcNAcylation of NOTCH1. EOGT mutations inhibit the NOTCH1 signalling pathway and cause several congenital developmental disorders, However, the role of EOGT in malignancies has not been reported.Methods:SHCBP1 and EOGT were identified as proto-oncogenes in PDAC by High-throughput sequencing and Cox regression analysis,and validated by Internal and External cohort and public databases. The function of SHCBP1 and EOGT was determined in vitro and in vivo, The underlying mechanism was investigated by Western blot,Immunofluorescence（IF），Co-immunoprecipitation (Co-IP), Chromatin immunoprecipitation (ChIP)，and luciferase analyses.Results: The expression of EOGT and SHCBP1 was significantly elevated and correlated with worse prognosis in PDAC patients. In vitro, SHCBP1 overexpression promoted pancreatic cancer cell proliferation,migration and invasion, while knocking down SHCBP1 and EOGT inhibited these malignant processes. In vivo data showed that SHCBP1 overexpression promoted xenograft growth and lung metastasis and shortened survival in mice,whereas knocking down either EOGT or SHCBP1 expression suppressed xenograft growth and metastasis and prolonged survival. Morever，EOGT and SHCBP1 enhance the O-GlcNAcylation of NOTCH1, subsequently promoting the nuclear localization of the Notch intracellular domain (NICD) and inhibiting the transcription of E-cadherin and P21 in pancreatic cancer cells.Conclusion:All in all，This research revealed that SHCBP1 and EOGT act as proto-oncogenes in PDAC by enhancing the O-GlcNAcylation of NOTCH1，Which provides a new field of vision for new therapeutic targets for pancreatic cancer.

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