scholarly journals Loss of 5′-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 492 ◽  
Author(s):  
Weder Pereira de Menezes ◽  
Viviane Aline Oliveira Silva ◽  
Izabela Natália Faria Gomes ◽  
Marcela Nunes Rosa ◽  
Maria Luisa Corcoll Spina ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
In Silico ◽  
Glioma Cell ◽  
Clinicopathological Features ◽  
Migration And Invasion ◽  
High Grade ◽  
Methylthioadenosine Phosphorylase ◽  
Frequent Event ◽  
High Grade Gliomas

The 5’-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients’ clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients’ clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP’s role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.

scholarly journals Long Intergenic Noncoding RNA 00152 Promotes Glioma Cell Proliferation and Invasion by Interacting with MiR-16

2018 ◽  
Vol 46 (3) ◽  
pp. 1055-1064 ◽  
Author(s):  
Xin Chen ◽  
Deheng Li ◽  
Yang Gao ◽  
Wei Tang ◽  
Lao IW ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cell ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Human Glioma Cell ◽  
Glioma Cell Lines ◽  
Glioma Cell Proliferation ◽  
Proliferation And Invasion

Background/Aims: Long noncoding RNAs (lncRNAs) are a novel class of protein-noncoding transcripts that are aberrantly expressed in multiple diseases including cancers. LINC00152 has been identified as an oncogene involved in many kinds of cancer; however, its expression pattern and function in human glioma remain unclear. Methods: Quantitative real-time polymerase chain reaction was carried out to measure LINC00152 expression in human glioma cell lines and tissues. CCK-8 and EdU assays were performed to assess cell proliferation, and scratch assays and Transwell assays were used to assess cell migration and invasion, respectively. Luciferase reporter assays were carried out to determine the interaction between miR-16 and LINC00152. In vivo experiments were conducted to assess tumor formation. Results: LINC00152 was found to be significantly upregulated in human glioma cell lines and clinical samples. Knockdown of LINC00152 suppressed glioma cell proliferation, migration, and invasion in vitro. In vivo assays in nude mice confirmed that LINC00152 knockdown inhibits tumor growth. Furthermore, mechanistic investigation showed that LINC00152 binds to miR-16 in a sequence-specific manner and suppresses its expression. miR-16 inhibition strongly attenuated LINC00152 knockdown–mediated suppressive effects on proliferation, migration, and invasion. Moreover, LINC00152 induced BMI1 expression by sponging miR-16; this effect further promoted glioma cell proliferation and invasion. Conclusion: We regard LINC00152 as an oncogenic lncRNA promoting glioma cell proliferation and invasion and as a potential target for human glioma treatment.

scholarly journals Proteolipid Protein 2 Overexpression Indicates Aggressive Tumor Behavior and Adverse Prognosis in Human Gliomas

2018 ◽  
Vol 19 (11) ◽  
pp. 3353 ◽  
Author(s):  
Yi-Hsuan Chen ◽  
Dueng-Yuan Hueng ◽  
Wen-Chiuan Tsai
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cell ◽  
Proteolipid Protein ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Human Gliomas ◽  
Advanced Tumor ◽  
Glioma Cell Lines ◽  
Aggressive Tumor

Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell lines and human glioma tissues. In addition, we used small interfering RNA (SiPLP2) and short hairpin RNA (shPLP2) to knockdown PLP2 expression in GBM8401 and LN229 glioma cell lines. After then, the alteration of PLP2 suppressed glioma cells behavior were examined by cell proliferation, wound healing, cell invasion, and colonies formation assays. Finally, the possible mechanism of PLP2 was analyzed by detecting the expression of the proteins related to cell-cycle checkpoints, cell-proliferative signaling factors, and cell-matrix interaction. Compared with normal brain cell lysates and mRNA, all glioma cell lines displayed PLP2 protein and mRNA overexpression. Besides, higher PLP2 IHC staining significantly correlated with more advanced tumor grades and poorer prognosis in human gliomas. Both siPLP2 transfected gliomas showed a clear inhibition of glioma cell proliferation, migration, and invasion as well as down-regulating p-p38, p-ERK, MMP-2, and MMP-9 expression. In conclusion, we successfully demonstrated that PLP2 overexpression played an oncogenic role in glioma development and aggressive tumor behavior.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

scholarly journals Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caihong Wen ◽  
Xiaoqing Feng ◽  
Honggang Yuan ◽  
Yong Gong ◽  
Guangsheng Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Pdcd4 Expression ◽  
Novel Target

Abstract Background Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation. Methods Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot. Results Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p. Conclusion Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.

scholarly journals An E3 Ubiquitin Ligase RNF139 Serves as a Tumor-Suppressor in Glioma

2021 ◽  
Author(s):  
Xiaofeng Chen ◽  
Weiping Kuang ◽  
Yong Zhu ◽  
Bin Zhou ◽  
Xiaosong Li ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Ubiquitin Ligase ◽  
Glioma Cell ◽  
Protein Modification ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Tissue Samples

AbstractGlioma is highly lethal because of its high malignancy. Ubiquitination, a type of ubiquitin-dependent protein modification, has been reported to play an oncogenic or tumor-suppressive role in glioma development, depending on the targets. Ring finger protein 139 (RNF139) is a membrane-bound E3 ubiquitin ligase serving as a tumor suppressor by ubiquitylation-dependently suppressing cell growth. Herein, we firstly confirmed the abnormal downregulation of RNF139 in glioma tissues and cell lines. In glioma cells, ectopic RNF139 overexpression could inhibit, whereas RNF139 knockdown could aggravate the aggressive behaviors of glioma cells, including hyperproliferation, migration, and invasion. Moreover, in two glioma cell lines, RNF139 overexpression inhibited, whereas RNF139 knockdown enhanced the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT serine/threonine kinase 1 (AKT). In a word, we demonstrate the aberration in RNF139 expression in glioma tissue samples and cell lines. RNF139 serves as a tumor-suppressor in glioma by inhibiting glioma cell proliferation, migration, and invasion and promoting glioma cell apoptosis through regulating PI3K/AKT signaling.

scholarly journals Long non-coding RNA CCDC183-AS1 acts AS a miR-589-5p sponge to promote the progression of hepatocellular carcinoma through regulating SKP1 expression

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
He Zhu ◽  
Hongwei Zhang ◽  
Youliang Pei ◽  
Zhibin Liao ◽  
Furong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Human Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Regulatory Relationship

Abstract Background Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1. Results Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC. Conclusions CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.

scholarly journals NOTCH3 Is a Prognostic Factor That Promotes Glioma Cell Proliferation, Migration and Invasion via Activation of CCND1 and EGFR

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77299 ◽  
Author(s):  
Mohammad A. Y. Alqudah ◽  
Supreet Agarwal ◽  
Maha S. Al-Keilani ◽  
Zita A. Sibenaller ◽  
Timothy C. Ryken ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Prognostic Factor ◽  
Glioma Cell ◽  
Migration And Invasion ◽  
Glioma Cell Proliferation

Downregulation of Sulfiredoxin (Srx) Suppressed Cell Proliferation Migration and Invasion Through Inhibiting Extracellular Signal-Regulated Kinase/Nrf2 Pathway in Hepatocellular Carcinoma

2021 ◽  
Vol 11 (11) ◽  
pp. 2137-2145
Author(s):  
Xuejuan Zhu ◽  
Danqian Lu
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Colony Formation ◽  
Migration And Invasion ◽  
Related Factor ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Nrf2 Signaling Pathway

Background: Sulfiredoxin (Srx) has been identified to play important roles in the development of various cancers. However, the precise effects and underlying mechanism of Srx on the progression of HCC are far from being fully understood. Materials and Methods: The abundances of Srx in THLE-2 cell and HCC cell lines were determined by western blot and RT-qPCR. Next, SK-Hep-1 cells were transfected with shRNA-Srx or shRNA-NC and treated with TBHQ (an extracellular signal-regulated kinase (ERK) activator) for functional experiments. Then, CCK8 and colony formation assays were used to determine cell proliferation and clone-forming abilities in vitro. Cell migration and invasion were assessed via wound healing and transwell assays. The expression of MMP2, MMP9 and key members in ERK/nuclear factor E2 related factor (Nrf2) signaling pathway was detected by performing western blot analysis. Results: We reported evidence that Srx was frequently up-regulated in HCC cell lines. Srx interference constrained cell proliferation, colony formation rate, migration and invasion of SK-Hep-1 cells. Moreover, mechanistic investigations indicated that Srx interference significantly inhibited the activation of ERK/Nrf2 signaling pathway, and ERK activator TBHQ can reverse the functions of Srx interference in SK-Hep-1 cells. Conclusion: Overall, Downregulation of Srx might impede HCC progression by suppressing ERK/Nrf2 signaling pathway. Findings in the current study reported the functional involvement and molecular mechanism of Srx in HCC, suggesting that Srx might have a potential therapeutic value in HCC treatment.

scholarly journals LncRNA-XIST interacts with miR-29c to modulate the chemoresistance of glioma cell to TMZ through DNA mismatch repair pathway

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Peng Du ◽  
Haiting Zhao ◽  
Renjun Peng ◽  
Qing Liu ◽  
Jian Yuan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mismatch Repair ◽  
Cell Lines ◽  
Glioma Cell ◽  
Dna Mismatch Repair ◽  
Tumor Biology ◽  
Glioma Cells ◽  
Dna Mismatch ◽  
Cell Proliferation Inhibition ◽  
Glioma Cell Lines

Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However, growing resistance to TMZ remains a major challenge for clinicians. Recent evidence emphasizes the key regulatory roles of non-coding RNAs (lncRNAs and miRNAs) in tumor biology, including the chemoresistance of cancers. However, little is known about the role and regulation mechanisms of lncRNA cancer X-inactive specific transcripts (XIST) in glioma tumorigenesis and chemotherapy resistance. In the present study, higher XIST expression was observed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. XIST knockdown alone was sufficient to inhibit glioma cell proliferation and to amplify TMZ-induced cell proliferation inhibition. Moreover, XIST knockdown can sensitize TMZ-resistant glioma cells to TMZ. XIST can inhibit miR-29c expression by directly targetting TMZ-resistant glioma cells. DNA repair protein O6-methylguanine-DNA methytransferase (MGMT) plays a key role in TMZ resistance; transcription factor specificity protein 1 (SP1), a regulator of DNA mismatch repair (MMR) key protein MSH6, has been reported to be up-regulated in TMZ-resistant glioma cell lines. In the present study, we show that XIST/miR-29c coregulates SP1 and MGMT expression in TMZ-resistant glioma cell lines. Our data suggest that XIST can amplify the chemoresistance of glioma cell lines to TMZ through directly targetting miR-29c via SP1 and MGMT. XIST/miR-29c may be a potential therapeutic target for glioma treatment.

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