scholarly journals Novel LncRNA OXCT1-AS1 indicates poor prognosis and contributes to tumorigenesis by regulating miR-195/CDC25A axis in glioblastoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chen Zhong ◽  
Qian Yu ◽  
Yucong Peng ◽  
Shengjun Zhou ◽  
Zhendong Liu ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Poor Prognosis ◽  
Expression Patterns ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Potential Mechanism ◽  
Potential Therapeutic Target ◽  
Tissue Samples ◽  
Cerna Network

Abstract Background Long noncoding RNAs (lncRNAs) contribute to multiple biological processes in human glioblastoma (GBM). However, identifying a specific lncRNA target remains a challenge. In this study, bioinformatics methods and competing endogenous RNA (ceRNA) network regulatory rules were used to identify GBM-related lncRNAs and revealed that OXCT1 antisense RNA 1 (OXCT1-AS1) is a potential therapeutic target for the treatment of glioma. Methods Based on the Gene Expression Omnibus (GEO) dataset, we identified differential lncRNAs, microRNAs and mRNAs and constructed an lncRNA-associated ceRNA network. The novel lncRNA OXCT1-AS1 was proposed to function as a ceRNA, and its potential target miRNAs were predicted through the database LncBase Predicted v.2. The expression patterns of OXCT1-AS1 in glioma and normal tissue samples were measured. The effect of OXCT1-AS1 on glioma cells was checked using the Cell Counting Kit 8 assay, cell colony formation assay, Transwell assay and flow cytometry in vitro. The dual-luciferase activity assay was performed to investigate the potential mechanism of the ceRNA network. Finally, orthotopic mouse models of glioma were created to evaluate the influence of OXCT1-AS1 on tumour growth in vivo. Results In this study, it was found that the expression of lncRNA OXCT1-AS1 was upregulated in both The Cancer Genome Atlas (TCGA) GBM patients and GBM tissue samples, and high expression of OXCT1-AS1 predicted a poor prognosis. Suppressing OXCT1-AS1 expression significantly decreased GBM cell proliferation and inhibited cell migration and invasion. We further investigated the potential mechanism and found that OXCT1-AS1 may act as a ceRNA of miR-195 to enhance CDC25A expression and promote glioma cell progression. Finally, knocking down OXCT1-AS1 notably attenuated the severity of glioma in vivo. Conclusion OXCT1-AS1 inhibits glioma progression by regulating the miR-195-5p/CDC25A axis and is a specific tumour marker and a novel potential therapeutic target for glioma treatment.

scholarly journals Novel LncRNA OXCT1-AS1 Indicates Poor Prognosis and Contributes to Tumorigenesis by Regulating miR-195/CDC25A Axis in Glioblastoma

2020 ◽  
Author(s):  
Chen Zhong ◽  
Qian Yu ◽  
Shengjun Zhou ◽  
Yucong Peng ◽  
Zhendong Liu ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Poor Prognosis ◽  
Cell Clone ◽  
Glioma Cells ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Potential Mechanism ◽  
Potential Therapeutic Target ◽  
Tissue Samples

Abstract BackgroundIt’s well known that long noncoding RNAs (lncRNAs) contribute to multiple biological processes of human glioblastoma (GBM). However, identifying a specific lncRNA target is still the major difficulty. In this study, bioinformatics methods and competing endogenous RNA network (ceRNA) regulatory rules was used to identify GBM related lncRNAs, and found OXCT1 antisense RNA 1 (OXCT1-AS1) may acted as a potential therapeutic target for treatment of glioma.MethodsBased on the Gene Expression Omnibus (GEO) date set, we identified differential lncRNAs, microRNAs and mRNAs and constructed a lncRNA associated ceRNA network.Novel lncRNA OXCT1-AS1 was proposed to exercise its function as a ceRNA, and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. The expression pattern of OXCT1-AS1 was measured in glioma and normal tissue samples. Effect of OXCT1-AS1 on glioma cells were checked by cell count kit 8 assay, cell clone formation assay, transwell assay and flow cytometry in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of ceRNA network. Finally, orthotopic mouse models of glioma was created to evaluate the influence of OXCT1-AS1 on tumor growth in vivo.ResultsIn this study, it was found that the expression of lncRNA OXCT1-AS1 is upregulated in both The Cancer Genome Atlas (TCGA) GBM cases and GBM tissue samples we collected, and a high expression of OXCT1-AS1 predicts poor prognosis of gliomas. Suppressing OXCT1-AS1 expression significantly decreased the proliferation of GBM cells and inhibited cell migration and invasion. We further investigated the potential mechanism and found OXCT1-AS1 may acted as a ceRNA of miR-195 to enhance CDC25A expression and attenuate glioma cells progression. Finally, knocking down of OXCT1-AS1 notably attenuated the severity of glioma in vivo.ConclusionOXCT1-AS1 inhibited glioma progression by regulating miR-195-5p/ CDC25A axis and can be a specific tumor marker and a novel potential therapeutic target for glioma treatment.

scholarly journals Identification of phosphoenolpyruvate carboxykinase 1 as a potential therapeutic target for pancreatic cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Xiao-ren Zhu ◽  
Shi-qing Peng ◽  
Le Wang ◽  
Xiao-yu Chen ◽  
Chun-xia Feng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Human Pancreatic Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Protein Levels ◽  
Pancreatic Cancer Cells

AbstractPancreatic cancer is the third leading cause of cancer-related mortalities and is characterized by rapid disease progression. Identification of novel therapeutic targets for this devastating disease is important. Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme of gluconeogenesis. The current study tested the expression and potential functions of PCK1 in pancreatic cancer. We show that PCK1 mRNA and protein levels are significantly elevated in human pancreatic cancer tissues and cells. In established and primary pancreatic cancer cells, PCK1 silencing (by shRNA) or CRISPR/Cas9-induced PCK1 knockout potently inhibited cell growth, proliferation, migration and invasion, and induced robust apoptosis activation. Conversely, ectopic overexpression of PCK1 in pancreatic cancer cells accelerated cell proliferation and migration. RNA-seq analyzing of differentially expressed genes (DEGs) in PCK1-silenced pancreatic cancer cells implied that DEGs were enriched in the PI3K-Akt-mTOR cascade. In pancreatic cancer cells, Akt-mTOR activation was largely inhibited by PCK1 shRNA, but was augmented after ectopic PCK1 overexpression. In vivo, the growth of PCK1 shRNA-bearing PANC-1 xenografts was largely inhibited in nude mice. Akt-mTOR activation was suppressed in PCK1 shRNA-expressing PANC-1 xenograft tissues. Collectively, PCK1 is a potential therapeutic target for pancreatic cancer.

scholarly journals Hsa_circRNA_002144 promotes growth and metastasis of colorectal cancer through regulating miR-615-5p/LARP1/mTOR pathway

2020 ◽  
Author(s):  
Mengqiong Wu ◽  
Cancan Kong ◽  
Manni Cai ◽  
Weiwei Huang ◽  
Yiming Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Target ◽  
Poor Prognosis ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Over Expression ◽  
Functional Assays ◽  
Cancer Intervention

Abstract CircRNAs (circular RNAs), recently identified as a critical regulator in tumorigenesis, participate in colorectal cancer (CRC) growth. However, role of hsa_circRNA_002144 in CRC was poorly understood. Firstly, hsa_circRNA_002144 showed significantly elevation in both of CRC tissues and cell lines, and suggested closely associated with poor prognosis in patients. Secondly, data from functional assays revealed that silence of hsa_circRNA_002144 inhibited CRC progression with reduced cell viability, proliferation, migration and invasion, while enhanced cell apoptosis. In addition, in vivo CRC growth and metastasis were also suppressed by knockdown of hsa_circRNA_002144. However, CRC progression was promoted with over-expression of hsa_circRNA_002144. Thirdly, hsa_circRNA_002144 colocalized with miR-615-5p in the cytoplasm of CRC cells, and decreased miR-615-5p expression. Moreover, miR-615-5p could target LARP1 (La ribonucleoprotein 1, translational regulator). Lastly, the suppressive effects of hsa_circRNA_002144 knockdown on CRC progression was reversed by LARP1 over-expression. In conclusion, hsa_circRNA_002144 could sponge miR-615-5p to promote CRC progression through regulation of LARP1, providing a therapeutic target for cancer intervention.

scholarly journals Downregulation of PRAME Suppresses Proliferation and Promotes Apoptosis in Hepatocellular Carcinoma Through the Activation of P53 Mediated Pathway

2018 ◽  
Vol 45 (3) ◽  
pp. 1121-1135 ◽  
Author(s):  
Hanzhang Zhu ◽  
Jingrui Wang ◽  
Junjie Yin ◽  
Bei Lu ◽  
Qijun Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Cell Apoptosis ◽  
Poor Prognosis ◽  
P53 Pathway ◽  
Tissue Samples ◽  
Potential Biomarker

Background/Aims: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism. Methods: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro. Further, we examined the relationship between PRAME and p53 pathway in vitro by using Western blotting. Finally, PRAME expression was detected to evaluate its correlation with p-p53 and p53 pathway related apoptotic proteins in xenograft tumor mouse model using immunohistochemistry. Results: PRAME expression was significantly higher in HCC tissues than in adjacent non-tumor tissues and their expression was positively correlated with alpha fetoprotein levels and tumor size. In addition, PRAME expression was associated with AJCC stage and is a potential biomarker of poor prognosis regarding 5-year overall survival in HCC. In vitro studies, we found that PRAME expression was higher in HCC cell lines than in normal hepatic cell line. Inhibited cell proliferation and increased cell apoptosis was observed in PRAME knockdown HCC cells. Futher, increased cell apoptosis was correlated with the proportion of cells in G0/G1 stage, activated p53 mediated apoptosis, and increased cyclin p21 expression. Xenograft analysis in nude mice also found that PRAME knockdown inhibited tumorigenesis while PRAME overexpression had opposite effect. Conclusions: In HCC, PRAME serves as a potential biomarker for poor prognosis and novel therapeutic target in treating this cancer. PRAME is a potential biomarker of poor prognosis in HCC. PRAME surpresses HCC cell death in vitro and in vivo by regulating p53 apoptotic signaling and may serve as a potential therapeutic target in HCC.

scholarly journals Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Hong-Guo Yang ◽  
Tian-peng Wang ◽  
Sheng-an Hu ◽  
Chao-zhou Hu ◽  
Cheng-hang Jiang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Intrahepatic Cholangiocarcinoma ◽  
Therapeutic Target ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Direct Binding ◽  
Proliferation And Metastasis ◽  
Long Non Coding Rna

Background: Small nucleolar RNA host gene 12 (SNHG12) is a newly identified long non-coding RNA (lncRNA) whose involvements have been explored in several cancers. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a-5p and Klotho.Methods: RT-PCR was performed to examine the expressions of SNHG12, miR-199a-5p and Klotho in ICC cells. Cell counting kit-8 (CCK-8), colony formation assays and transwell assays were applied to analyze the proliferation, migration and invasion of ICC cells. Luciferase assays, RIP assays and RNA pull-down assays were carried out to demonstrate the direct binding relationships among SNHG12, miR-199a-5p and Klotho. The xenograft nude models were applied to test the effects of SNHG12 on ICC tumor growth.Results: The expression of SNHG12 and Klotho was distinctly increased in ICC cells, while miR-199a-5p expressions were decreased. Functionally, the silence of SNHG12 inhibited the proliferation and metastasis of ICC cells, while miR-199a-5p overexpression exhibited an opposite result. Mechanistically, Knockdown of SNHG12 significantly suppressed the expressions of miR-199a-5p by sponging it, and then increased Klotho expression. The final in vivo experiments suggested that the silence of SNHG12 distinctly inhibited tumor growth.Conclusion: Our findings indicated that SNHG12 inhibited cell proliferation and metastasis process of ICC cells through modulating the miR-199a-5p/Klotho axis and it is expected to become a potential therapeutic target for ICC.

scholarly journals NLRP3 Overexpression Associated With Poor Prognosis and Presented as an Effective Therapeutic Target in Osteosarcoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhen Huang ◽  
Hui Chen ◽  
Shenglin Wang ◽  
Hongxiang Wei ◽  
Xinwen Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Therapeutic Target ◽  
Poor Prognosis ◽  
Tumor Formation ◽  
Cell Counting ◽  
Biological Behavior ◽  
Receptor Protein ◽  
Cell Cycle Distribution ◽  
Osteosarcoma Cell

Despite the development of diagnostic and treatment strategies, the survival outcome of patients with osteosarcoma remains poor. Nod-like receptor protein 3 (NLRP3) plays a crucial role in the inflammasome pathway, which is related to the progression of various tumors. However, the effect of NLRP3 on osteosarcoma has not yet been well explored. Our study aimed to investigate the role of NLRP3 in the malignant biological behavior of osteosarcoma as well as its therapeutic value. Immunohistochemistry was applied to investigate the NLRP3 expression in osteosarcoma and osteochondroma specimens. Cell Counting Kit-8, colony formation, wound healing, transwell, and flow cytometry assays were used to explore the contribution of NLRP3 to the proliferation, migration, invasion, apoptosis and cell cycle distribution of osteosarcoma cells in vitro. Western blot was performed to evaluate the expression of NLRP3 and the related proteins in osteosarcoma cell lines after the blockade of NLRP3 using CY-09 and lentivirus intervention. Furthermore, tumor formation assay was used to analyze the effect of NLRP3 on the growth of osteosarcoma in vivo. The results showed that the NLRP3 protein was overexpressed in osteosarcoma, which was independently correlated with the poor prognosis of patients. Moreover, NLRP3 suppression by the inhibitor of CY-09 or lentivirus-induced gene knockdown inhibited the cell proliferation, migration, invasion and promoted the cell apoptosis and G1 cell cycle arrest in osteosarcoma via targeting the inflammasome pathway. Our in vivo results confirmed that the inhibition of NLRP3 suppressed the tumor formation of osteosarcoma. In conclusion, NLRP3 may be regarded as an independent prognostic biomarker and a potential therapeutic target for osteosarcoma.

CCNE1 promotes progression and is associated with poor prognosis in lung adenocarcinoma

2021 ◽  
Vol 22 ◽  
Author(s):  
Guoliang Ma ◽  
Lulu Yang ◽  
Jing Dong ◽  
Lili Zhang
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Annexin V ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Cyclin E1 ◽  
Tumor Growth And Metastasis

Background : Mounting evidence has shown that Cyclin E1 (CCNE1) facilitates various carcinoma progression, but its function in lung adenocarcinoma (LUAD) remains unclear. Objective: Our study aims to explore the significance of CCNE1 in clinical progression and study its biological functions in LUAD. Methods: CCNE1 expressions in LUAD specimens and cells were detected through quantitative realtime polymerase chain reaction (qRT-RCR) and western blot. An immunohistochemistry technique was used to detect CCNE1 expression to explore its association with clinical parameters. The LUAD cells with stable knockdown of CCNE1 were constructed by small interfering RNA. The effect of CCNE1 on LUAD cells proliferation and apoptosis was evaluated through Cell Counting Kit-8 (CCK-8), colony formation, and Annexin V/propidium iodide (AV-PI) assays, respectively. The cell migration and invasion were evaluated by Wound-healing and Transwell assays, respectively. The xenograft and lung metastasis mouse models were introduced to analyze how CCNE1 knockdown affects tumor growth and tumor metastasis. Results: CCNE1 expression was upregulated in LUAD tissue and cells. CCNE1 knockdown inhibited LUAD cellular malignant behavior in vitro and reduced tumor growth and metastasis in vivo. High expression of CCNE1 was correlated with big tumor size, cancer stage, lymph node metastasis, and poor prognosis. Conclusions: CCNE1 overexpression promotes LUAD growth, metastasis, and forebode poor prognosis: it can serve as a new prognostic marker of LUAD.

scholarly journals CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Guanqun Huang ◽  
Min Liang ◽  
Haiyan Liu ◽  
Jianhong Huang ◽  
Peiqing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Expression Patterns ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Biological Functions ◽  
Competing Endogenous Rna ◽  
Direct Target

AbstractCircular RNAs (circRNAs) have confirmed to participate in diverse biological functions in cancer. However, the expression patterns of circRNAs on hepatocellular carcinoma (HCC) remains unclear. In the present study, we clarified that hsa_circRNA_104348 was dramatically upregulated in HCC tissues and cells. Patients with HCC displaying high hsa_circRNA_104348 level possessed poor prognosis. Has_circ_104348 facilitated proliferation, migration, and invasion, meanwhile suppressed apoptosis of HCC cell. Furthermore, hsa_circRNA_104348 directly targeted miR-187–3p, could regulate miR-187-3p to affect proliferation, migration, invasion, and apoptosis of HCC cells, and may have effect on Wnt/β-catenin signaling pathway. Moreover, RTKN2 could be a direct target of miR-187-3p. In addition, knockdown of hsa_circRNA_104348 attenuated HCC tumorigenesis and lung metastasis in vivo. Taken together, these findings indicated that circular RNA hsa_circRNA_104348 might function as a competing endogenous RNA (ceRNA) to promotes HCC progression by targeting miR-187–3p/RTKN2 axis and activating Wnt/β-catenin pathway.

USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer

2020 ◽  
Vol 20 (9) ◽  
pp. 689-699
Author(s):  
Xuemeng Lei ◽  
Xukun Li ◽  
Hongyan Chen ◽  
Zhihua Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Deubiquitinating Enzymes ◽  
Potential Therapeutic Target ◽  
Kaplan Meier ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Background: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear. Objective: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation. Methods: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice. Results: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy. Conclusion: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

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