scholarly journals Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shang-Ju Tang ◽  
Guo-Rong You ◽  
Joseph T. Chang ◽  
Ann-Joy Cheng
Keyword(s):  
Neck Cancer ◽  
Clinical Sample ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Head Neck Cancer ◽  
Systematic Analysis ◽  
Invasion And Migration ◽  
Cancer Aggressiveness ◽  
And Migration ◽  
Rnai Technique

Head and neck cancer (HNC) is one of the most prevalent cancers worldwide, accounting for approximately 5% of all cancers. While the underlying molecules and their pathogenetic mechanisms in HNC have yet to be well elucidated, recent studies have shown that dysregulation of lncRNAs may disrupt the homeostasis of various biological pathways. However, the understanding of lncRNAs in HNC is still limited by the lack of expression profiling. In the present study, we employed a systematic strategy to identify a panel of lncRNA associated with HNC. A cancer-related lncRNA profile PCR array was screened to explore potential molecules specific for HNC. A total of 55 lncRNAs were found to be dysregulated in HNC cells when compared to normal keratinocytes. Further analysis of the prognostic significance using The Cancer Genome Atlas (TCGA) database revealed 15 lncRNAs highly correlated with overall survival in HNC patients. Additionally, clinical sample expression analysis of the TCGA-HNSC cohort revealed 16 highly dysregulated lncRNAs in HNC, resulting in a combined 31-lncRNA signature panel that could predict prognosis. Validation of these molecules confirmed the considerable level of altered expressions in HNC cells, with XIST, HOXA11-AS, TSIX, MALAT1, WT1-AS, and IPW being the most prominently dysregulated. We further selected a molecule from our panel (XIST) to confirm the validity of these lncRNAs in the regulation of cancer aggressiveness. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses demonstrated that XIST participated in various cancer-related functions, including cell proliferation and metastasis. XIST silencing with the RNAi technique substantially reduced invasion and migration in several HNC cell lines. Thus, our study defined a 31-lncRNA panel as prognostic signatures in HNC. These perspective results provide a knowledge foundation for further application of these molecules in precision medicine.

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

scholarly journals ALG3 Contributes to the Malignant Biological Properties of Oral Squamous Cell Carcinoma Cells Through Regulating CDK-Cyclin Pathway

2020 ◽  
Author(s):  
Peihong Shao ◽  
Chengshi Wei ◽  
Yun Wang
Keyword(s):  
Western Blot ◽  
Colony Formation ◽  
Enrichment Analysis ◽  
Biological Properties ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Invasion And Migration ◽  
Elevated Expression ◽  
Cancer Genome Atlas ◽  
And Migration

Abstract Background: In this study, we planned to investigate the function and potential mechanisms of Alpha-1,3-mannosyltransferase (ALG3) in oral squamous cell carcinoma (OSCC). Methods: Data from The Cancer Genome Atlas (TCGA) was used to analyze ALG3 expression and its effect on the prognosis of patients with OSCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was applied to explore the signaling pathways related to ALG3. In OSCC cells, ALG3 expression was measured by qPCR and western blot. Cell counting kit-8, colony formation, and transwell assays were implemented to detect the effects of ALG3 on the malignant biological properties OSCC cells. The expression of key proteins related to CDK-Cyclin pathway was detected by western blot. Results: The expression of ALG3 in OSCC samples was higher than that of the control samples, and the increase of ALG3 expression was related to unfavorable prognosis of OSCC patients. Additionally, the elevated expression of ALG3 was associated with pathological stage, lymph node metastasis and primary lesion in OSCC patients. ALG3 depletion blocked the growth, colony formation, invasion and migration of OSCC cells, while over-expression ALG3 reversed these phenomena. Moreover, exhaustion of ALG3 resulted in decreased expression of MCM7, CCNB2, CDK1 and PCNA, while these phenomena were inversed after ALG3 up-regulation. Conclusions: The enhancement of ALG3 expression promoted the aggressive biological behaviors of OSCC cells probably by promoting CDK-Cyclin pathway.

scholarly journals Homeodomain-containing gene 10 inhibits cell apoptosis and promotes cell invasion and migration in osteosarcoma cell lines

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769756 ◽  
Author(s):  
Wen Xiong ◽  
Quan Zhou ◽  
Gang Liu ◽  
Xiang-Sheng Liu ◽  
Xin-Yu Li
Keyword(s):  
Cell Apoptosis ◽  
Bone Cyst ◽  
Molecular Target ◽  
The Cancer Genome Atlas ◽  
Osteosarcoma Cell ◽  
Invasion And Migration ◽  
Mg63 Cells ◽  
And Migration

Homeodomain-containing gene 10 (HOXC10) belongs to the homeobox family, which encodes a highly conserved family of transcription factors that plays an important role in morphogenesis in all multicellular organisms. Altered expressions of HOXC10 have been reported in several malignancies. This study was aimed to reveal the expression profile of HOXC10 in osteosarcoma and evaluated whether HOXC10 is a molecular target for cancer therapy. We found that HOXC10 was up-regulated in osteosarcoma tissues compared with bone cyst specimens from The Cancer Genome Atlas database. Osteosarcoma MG63 cells were infected with HOXC10 shRNA expressing vector, and 143B cells were infected with HOXC10 expressing vector. We found that reduced expression of HOXC10 markedly impaired the ability of proliferation, invasion, and migration, and promoted cell apoptosis in vitro and in vivo. Up-regulated expression of HOXC10 promoted the proliferation, invasion, and migration, and inhibited apoptosis of 143B cells. Additionally, HOXC10 regulated apoptosis and migration via modulating expression of Bax/Bcl-2, caspase-3, MMP-2/MMP-9, and E-cadherin in both MG63 and 143B cells and in vivo. These results indicated that HOXC10 might be a diagnostic marker for osteosarcoma and could be a potential molecular target for the therapy of osteosarcoma.

scholarly journals LINC01268 and CTB-31O20.2 as Prognostic and Functional Protective Immune Related lncRNAs in Glioblastoma

2021 ◽  
Author(s):  
Dong-Hui Liu ◽  
Xiu Yang ◽  
Han Meng ◽  
Gui Yun Zhang ◽  
Shanghang Shen
Keyword(s):  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Invasion And Migration ◽  
Kaplan Meier ◽  
Competitive Endogenous Rnas ◽  
The Central Nervous System ◽  
And Migration ◽  
Immune Related Genes

Abstract Glioblastoma (GBM) is the most common and deadly tumor in the central nervous system. Recent studies illuminated that long noncoding RNAs (lncRNAs) serve as competitive endogenous RNAs (ceRNAs) and play an important role in GBM by regulating immune responses. Here, GBM datasets from TCGA database were analyzed to obtain 356 significantly differentially expressed lncRNAs (DE-lncRNAs), 4951 DE-mRNAs, and 34 DE-miRNAs in GBM, respectively. For mRNAs, 369 DE-mRNAs were identified as immune-related genes in Immport database. For DE-lncRNAs, univariate analysis identified 39 DE-lncRNAs with prognostic significance, and 9 DE-lncRNAs are included in ImmLnc database. Then, combined analysis was conducted, by integrating 9 immune related DE-lncRNAs, 369 immune related DE-mRNAs and 34 DE-miRNAs, and generated a ceRNA network composed of 2 upregulated lncRNAs (LINC01268 and CTB-31O20.2), 3 downregulated miRNAs and 5 upregulated mRNAs. Then we focused on LINC01268 and CTB-31O20.2, and Kaplan-Meier survival, univariate and multivariate Cox regression analysis showed that LINC01268 and CTB-31O20.2 serve as independent protective prognostic markers in GBM. Finally, LINC01268 and CTB-31O20.2 overexpression was conducted in GBM cell U251. CCK8, transwell and scratch healing assay indicated that LINC01268 and CTB-31O20.2 inhibits GBM cell line U251 proliferation, invasion and migration. To sum up, LINC01268 and CTB-31O20.2 are independent prognostic immune related markers, and reduces cancer cell proliferation and metastasis in GBM.

scholarly journals circEPS15 Overexpression in Hepatocellular Carcinoma Modulates Tumor Invasion and Migration

2020 ◽  
Author(s):  
Maolin Tian ◽  
Gang Li ◽  
Bin Jiang ◽  
Sadula Abuduhaibaier ◽  
Dianrong Xiu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Tumor Invasion ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
Qrt Pcr ◽  
Cerna Network ◽  
And Migration

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Recent evidence indicates that circular RNAs (circRNAs) play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown.Methods: Circular RNA microarrays were performed using three pathologically diagnosed HCC samples and their paired adjacent normal liver tissues. Cell invasion, migration, cell cycle, and apoptosis after circRNA overexpression were measured using a transwell culture system, a wound healing assay, and flow cytometry . Full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag were inserted inside a circular expression vector. Western blotting was used to confirm circEPS15 expression and the requirement of internal ribosomal entry site (IRES) elements within the circRNA. The miRNA and mRNA expression profiles were obtained by analyzing data retrieved from The Cancer Genome Atlas (TCGA) database. We then constructed a ceRNA network of mRNAs, miRNAs, and circEPS15. Using tissue samples from own patients, we also verified certain analytical results with quantitative real-time PCR (qRT-PCR).Results: The expression of circEPS15 was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Overexpression of circEPS15 suppressed tumor invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, but it had no effect on cell apoptosis. ceRNA analysis and qRT-PCR showed that there might be a circRNA (circEPS15)-miRNA (miR-24-3p)-mRNA (CIDEA) network in HCC. The spanning junction open reading frame in circEPS15 driven by IRES encoded a novel protein.Conclusions: Endogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encoding a functional protein.

LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway

2019 ◽  
Vol 41 (9) ◽  
pp. 1273-1281 ◽  
Author(s):  
Kai Fang ◽  
Caixia Hu ◽  
Xiufen Zhang ◽  
Yafei Hou ◽  
Danfeng Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
P38 Mapk ◽  
The Cancer Genome Atlas ◽  
Mitogen Activated Protein Kinase ◽  
High Expression ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Mapk Signalling ◽  
And Migration

Abstract Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared with the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with estrogen receptor-negative, progesterone receptor-negative, advanced tumour-node-metastasis stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 mitogen-activated protein kinase (MAPK) gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

scholarly journals Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Shutao Pan ◽  
Ming Shen ◽  
Min Zhou ◽  
Xiuhui Shi ◽  
Ruizhi He ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Invasion And Migration ◽  
Cancer Aggressiveness ◽  
And Migration

AbstractDysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.

scholarly journals Functional implications of PABPC1 in the development of ovarian cancer

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 805-815
Author(s):  
Cong Feng ◽  
Yan-Hua Han ◽  
Na Qi ◽  
Jia Li ◽  
Qing-Hua Sheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Data Set ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Abstract This research aimed to probe the expression characteristics of poly(A)-binding protein cytoplasmic 1 (PABPC1) and its role on the phenotype of ovarian cancer (OC) cells and to further investigate the possible underlying mechanism. The expression of PABPC1 was analyzed according to the data from gene expression omnibus, The Cancer Genome Atlas (TCGA) and Oncomine databases and the RNA sequencing data set from TCGA were downloaded for evaluating the prognostic values. We revealed that compared with the healthy samples, PABPC1 was upregulated in OC samples. High expression of PABPC1 had a connection with a shorter survival for patients with OC. Loss and gain of function assays revealed that silencing PABPC1 significantly suppressed the viability, invasion and migration of SK-OV-3 cells, while PABPC1 overexpression in A2780 cells showed the reverse outcomes. Moreover, Western blot demonstrated that silencing PABPC1 notably inactivated the epithelial–mesenchymal transition (EMT) process, while upregulation of PABPC1 promoted the mitigation of epithelial phenotype and the acquisition of mesenchymal phenotype. Taken together, PABPC1 was upregulated in OC cells and served as a carcinogene to promote the OC cell growth and invasion partly by modulating the EMT process, which implied that PABPC1 might be considered as a useful biomarker for OC therapeutics.

scholarly journals circEPS15 Overexpression in Hepatocellular Carcinoma Modulates Tumor Invasion and Migration

2021 ◽  
Author(s):  
Maolin Tian ◽  
Gang Li ◽  
Bin Jiang ◽  
Abuduhaibaier Sadula ◽  
Dianrong Xiu ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Circular Rnas ◽  
Functional Protein ◽  
Entry Site ◽  
Poor Overall Survival ◽  
Invasion And Migration ◽  
Cerna Network ◽  
And Migration

Abstract BackgroundHepatocellular carcinoma (HCC) is one kind of the leading causes of cancer-related deaths in the world. Recent evidence indicates that circular RNAs (circRNAs) play important roles in tissue development, gene transcription, signal regulation and tumorigenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown.MethodscircRNAs microarrays wereperformed using three pathologically diagnosed HCC samples and their paired adjacent normal liver tissues. Cell invasion, migration, cycle, and apoptosis post circRNA overexpression were measured using a transwell culture system, a wound healing assay, and flow cytometry. Full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag were inserted into a circular expression vector. Western blotting was used to confirm circEPS15 expression and the requirement of internal ribosomal entry site (IRES) elements within the circRNA. The miRNA and mRNA expression profiles were obtained by analyzing data retrieved from The Cancer Genome Atlas (TCGA) database. We then constructed a ceRNA network ofcircEPS15, miRNAs, and mRNAs. ResultsThe expression of circEPS15 was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Overexpression of circEPS15 suppressed tumor invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, yet had no effect on cell apoptosis. ceRNA analysis and qRT-PCR results suggest a possible circRNA (circEPS15)-miRNA (miR-24-3p)-mRNA (CIDEA) network in HCC. The spanning junction open reading frame in circEPS15 driven by IRES encoded a novel protein.ConclusionsEndogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encoding a functional protein.

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