scholarly journals MBRS-72. MiR-212 FUNCTIONS AS A TUMOR SUPPRESSOR GENE IN GROUP 3 MEDULLOBLASTOMA VIA TARGETING NUCLEAR FACTOR I/B (NFIB)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii411-iii411
Author(s):  
Naveenkumar Perumal ◽  
Ranjana Kanchan ◽  
Pranita Atri ◽  
Ramakanth Venkata ◽  
Ishwor Thapa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Luciferase Assay ◽  
Multi Drug Resistance ◽  
Migration And Invasion ◽  
Stem Cell Markers ◽  
Tumor Cell Proliferation ◽  
Group 3

Abstract Medulloblastoma (MB), the most frequent malignant pediatric brain tumor is divided into four primary subgroups, i.e. wingless-type (WNT), sonic hedgehog (SHH), group 3, and group 4. Haploinsufficiency of chromosome 17p13.3 and c-myc amplification distinguish high-risk group 3 tumors and are associated with rapid recurrence and early mortality. We sought to identify the role of miR-212, which resides on chromosome 17p13.3, in the pathophysiology of group 3 medulloblastoma. RNA expression analyses revealed dramatically reduced levels of miR-212 in group 3 tumors and cell lines mainly through epigenetic silencing via histone modification (deacetylation). Restoring in vitro expression reduced tumor cell proliferation with decreased p-AKT and p-ERK levels, colony formation, migration and invasion in group 3 MB. Interestingly, a shift in differential c-myc phosphorylation (from serine-62 to threonine-58) was noted, resulting in reduced total c-myc levels, concurrent with elevated cellular apoptosis. In turn, pro-apoptotic binding partners of c-myc, i.e. Bin-1 and P19ARF, were upregulated in these cells. A dual luciferase assay confirmed direct targeting of miR-212 to NFIB, a nuclear transcription factor implicated in metastasis and recurrence. Concurrently, increased expression of NFIB was confirmed in group 3 MB tumors with poor survival in high NFIB-expressing patients. Transient NFIB silencing in vitro reduced tumor cell proliferation, migration and invasion, and medullosphere formation along with a reduction in stem cell markers (Nanog, Oct4, Sox2, CD133) and the multi-drug resistance maker, ABCG2. Taken together, these results substantiate the tumor suppressive role of miR-212 in group 3 medulloblastomas and provide a potential new therapeutic target, NFIB.

scholarly journals BIOL-07. MIR-212 FUNCTIONS AS A TUMOR SUPPRESSOR GENE IN GROUP 3 MEDULLOBLASTOMA VIA TARGETING NUCLEAR FACTOR I/B (NFIB)

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i4-i4
Author(s):  
Naveenkumar Perumal ◽  
Ranjana Kanchan ◽  
David Doss ◽  
Pranita Atri ◽  
Ramakanth Chirravuri Venkata ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Tumor Cell ◽  
Colony Formation ◽  
Tumor Recurrence ◽  
Migration And Invasion ◽  
Tumor Cell Proliferation ◽  
Group 3

Abstract Medulloblastoma (MB), the most frequent malignant pediatric brain tumor is subdivided into four primary subgroups, i.e. wingless-type (WNT), sonic hedgehog (SHH), group 3, and group 4. Haploinsufficiency of chromosome 17p13.3 and c-myc amplification distinguish high-risk group 3 tumors, which are associated with rapid metastasis, recurrence and early mortality. We sought to identify the role of miR-212, which resides on chromosome 17p13.3, in the pathophysiology of group 3 MB. RNA expression analyses revealed dramatically reduced levels of miR-212 in group 3 tumors and cell lines mainly through epigenetic silencing via histone modifications (deacetylation). Restoring in vitro miR-212 expression reduced tumor cell proliferation, colony formation, wound healing, migration and invasion with decreased p-AKT and p-ERK levels in group 3 MB cell lines. Interestingly, a shift in differential c-myc phosphorylation (from serine-62 to threonine-58) was also discovered with miR-212 expression, resulting in reduced total c-myc levels, concurrent with elevated cellular apoptosis. In turn, pro-apoptotic binding partners of c-myc, i.e. Bin-1 and P19ARF, were upregulated in these cells. These findings were recapitulated in stable inducible miR-212 expressing tumor cells. Using a combination of transcriptomic data and a dual luciferase assay, we isolated an important oncogenic target of miR-212, i.e, NFIB, a nuclear transcription factor implicated in metastasis and recurrence. Increased expression of NFIB was confirmed in group 3 tumors, with poor survival shown in high NFIB-expressing patients. As prior, transient NFIB silencing in vitro reduced not only tumor cell proliferation, colony formation, wound healing, migration and invasion, but also medullosphere formation along with decreased expression of stem cell markers (Nanog, Oct4, Sox2, CD133), confirming its role in tumor recurrence possibly via augmenting tumor stemness. Taken together, these results substantiate the tumor suppressive role of miR-212 in group 3 MB and provide a potential new oncogenic target implicated in tumor recurrence, NFIB.

scholarly journals MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting Nuclear Factor I/B (NFIB)

2021 ◽  
Author(s):  
Naveenkumar Perumal ◽  
Ranjana K. Kanchan ◽  
David Doss ◽  
Noah Bastola ◽  
Pranita Atri ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Colony Formation ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Stem Cell Markers ◽  
Cancer Cell Proliferation ◽  
Group 3

ABSTRACTBackgroundMedulloblastoma (MB), the most frequent malignant pediatric brain tumor, is subdivided into four primary subgroups, wingless-type (WNT), sonic hedgehog (SHH), group 3, and group 4. Haploinsufficiency of chromosome 17p13.3 and c-Myc amplification distinguish high-risk group 3 tumors associated with rapid metastasis, recurrence and early mortality. We sought to identify the role of miR-212-3p, which resides on chromosome 17p13.3, in the pathophysiology of group 3 MB.MethodsWe first determined miR-212-3p expression in group 3 MB using several publicly-available datasets with confirmatory studies in vitro. We then identified epigenetic regulation by studying methylation and HDAC modifications along the promoter region. We used two systems for expression restoration, i.e. transient transfection or stable induction, to delineate miR-212-3p’s tumor suppressive and biochemical properties via assays assessing cancer proliferation, migration, invasion, colony formation, along with cell cycle and apoptosis analyses. We then compared MB and miR target databases to isolate a putative target whose biochemical and oncogenic properties were similarly elucidated using either transient silencing of target expression or stable induction of miR-212-3p.ResultsRNA expression analyses revealed dramatically reduced miR-212-3p levels in group 3 tumors and cell lines mainly through epigenetic silencing via histone modifications. Restoring miR-212-3p expression reduced in vitro cancer cell proliferation, migration, colony formation, and wound healing. Elevated miR-212-3p levels shifted c-Myc phosphorylation (from serine-62 to threonine-58), triggering destabilization and degradation; concurrently, its pro-apoptotic binding partners, i.e., Bin-1 and P19ARF, were upregulated with subsequent elevated apoptotic signals. Using a combination of transcriptomic data and dual luciferase assay, we isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors, with poor survival shown in high-expressing patients. Transient NFIB silencing in vitro reduced cancer cell proliferation, colony formation, migration, and invasion. Concurrently, in group 3 MB cells, reduced medullosphere formation along with decreased expression of stem cell markers (Nanog, Oct4, Sox2, CD133) were noted.ConclusionThese results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and provide a potential therapeutic oncogenic target implicated in metastasis and tumor recurrence.

scholarly journals MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Naveenkumar Perumal ◽  
Ranjana K. Kanchan ◽  
David Doss ◽  
Noah Bastola ◽  
Pranita Atri ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cancer Cell ◽  
Migration And Invasion ◽  
Stem Cell Markers ◽  
Cancer Cell Proliferation ◽  
Group 3

AbstractHaploinsufficiency of chromosome 17p and c-Myc amplification distinguish group 3 medulloblastomas which are associated with early metastasis, rapid recurrence, and swift mortality. Tumor suppressor genes on this locus have not been adequately characterized. We elucidated the role of miR-212-3p in the pathophysiology of group 3 tumors. First, we learned that miR-212-3p undergoes epigenetic silencing by histone modifications in group 3 tumors. Restoring its expression reduced cancer cell proliferation, migration, colony formation, and wound healing in vitro and attenuated tumor burden and improved survival in vivo. MiR-212-3p also triggered c-Myc destabilization and degradation, leading to elevated apoptosis. We then isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors and associated with poor survival. NFIB silencing reduced cancer cell proliferation, migration, and invasion. Concurrently, reduced medullosphere formation and stem cell markers (Nanog, Oct4, Sox2, CD133) were noted. These results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and identify a novel oncogenic target implicated in metastasis and tumor recurrence.

scholarly journals LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuhong Dai ◽  
Ning Li ◽  
Ming Zhou ◽  
Yue Yuan ◽  
Ding Yue ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Regulatory Loop

AbstractThe treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3′-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR‐372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.

Does hysteroscopy promote tumor cell proliferation in endometrial cancer?

2021 ◽  
Vol 50 (3) ◽  
pp. 28-30
Author(s):  
A. F. Urmancheeva ◽  
D. R. Zel'dovich ◽  
M. S. Shushania ◽  
A. V. Safronov
Keyword(s):  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Comparative Analysis ◽  
Tumor Cell ◽  
Tumor Cell Proliferation ◽  
Tumor Cell Dissemination ◽  
Cytological Investigation ◽  
Promote Tumor Cell ◽  
Cell Dissemination

Peritoneal cytological investigation was carried out inpatients with endometrial cancer, who were subjected to hysteroscopy before the operation (37patients) or were operated on without hysteroscopy. Comparative analysis of the data didnt reveal the role of hysteroscopy in tumor cell dissemination.

miR-369-3p serves as prognostic factor and regulates cancer progression of hepatocellular carcinoma

2021 ◽  
Author(s):  
Can Chen ◽  
Yi Zong ◽  
Jiaojiao Tang ◽  
Ruisheng Ke ◽  
Lizhi Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Reverse Transcription Pcr ◽  
Huh7 Cells

Background: The aim of this study was to investigate the role of miR-369-3p in hepatocellular carcinoma (HCC). Materials & methods: The expression levels of miR-369-3p were detected using the quantitative real-time reverse transcription-PCR analysis. The cell counting kit-8 and transwell assays were used to explore the effects of miR-369-3p on cell proliferation, migration and invasion of HCC cells. Results: The miR-369-3p expression was downregulated in HCC tissues and cell lines, in comparison to the normal controls, respectively. In vitro, overexpression of miR-369-3p in Hep 3B and Huh7 cells inhibited cell proliferation, migration and invasion. SOX4 was a direct target of miR-369-3p. Conclusion: Our results suggested that miR-369-3p may be a tumor suppressor in HCC by targeting SOX4.

scholarly journals BAG3 contributes to HGF-mediated cell proliferation, migration, and invasion via the Egr1 pathway in gastric cancer

2018 ◽  
Vol 105 (1) ◽  
pp. 63-75
Author(s):  
Jae Chang Lee ◽  
Sung Ae Koh ◽  
Kyung Hee Lee ◽  
Jae-Ryong Kim
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Protein Levels ◽  
Dependent Pathway

Introduction: Bcl2-associated athanogene 3 (BAG3) is elevated in several types of cancers. However, the role of BAG3 in progression of gastric cancer is unknown. Therefore, the present study aims to find out the role of BAG3 in hepatocyte growth factor (HGF)–mediated tumor progression and the molecular mechanisms by which HGF regulates BAG3 expression. Methods: BAG3 mRNA and protein were measured using reverse transcription polymerase chain reaction and Western blot in the 2 human gastric cancer cell lines, NUGC3 and MKN28, treated with or without HGF. The effects of BAG3 knockdown on cell proliferation, cell invasion, and apoptosis were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the in vitro 2-chamber invasion assay, and flow cytometry in BAG3 short hairpin RNA (shRNA)–transfected cells and control cells. The signaling pathways involved in BAG3 that are regulated by HGF were analyzed. The chromatin immunoprecipitation assay was used to determine binding of Egr1 to the BAG3 promoter. Results: BAG3 mRNA and protein levels were increased following treatment with HGF. HGF-mediated BAG3 upregulation increased cell proliferation and cell invasion; however, it decreased apoptosis. HGF-mediated BAG3 upregulation is regulated by an ERK and Egr1-dependent pathway. BAG3 may have an important role in HGF-mediated cell proliferation and metastasis in gastric cancer through an ERK and Egr1-dependent pathway. Conclusion: This pathway may provide novel therapeutic targets and provide information for further identification of other targets of therapeutic significance in gastric cancer.

scholarly journals The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome

2020 ◽  
Author(s):  
Iolanda Ferro ◽  
Jacopo Gavini ◽  
Lisamaria Bracher ◽  
Marc Landolfo ◽  
Daniel Candinas ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Chemotherapy Resistance ◽  
Autophagic Flux ◽  
Tumor Cell Proliferation ◽  
Apoptosis Resistance ◽  
Knock Out ◽  
Vault Rna

AbstractThe small non-coding vault RNA (vtRNA) 1-1 has been shown to confer apoptosis resistance in several malignant cell lines and also to modulate the autophagic flux in hepatocytes, thus highlighting its pro-survival role. Here we describe a new function of vtRNA1-1 in regulating in vitro and in vivo tumor cell proliferation, tumorigenesis and chemoresistance. By activating extracellular signal-regulated kinases (ERK 1/2), vtRNA1-1 knock-out (KO) inhibits transcription factor EB (TFEB), leading to a downregulation of the coordinated lysosomal expression and regulation (CLEAR) network genes and lysosomal compartment dysfunction. Pro-tumorigenic pathways dysregulation and decreased lysosome functionality potentiate the anticancer effect of conventional targeted cancer drugs in the absence of vtRNA1-1. Finally, vtRNA1-1 KO-reduced lysosomotropism, together with a higher intracellular compound availability, significantly reduced tumor cell proliferation in vitro and in vivo. These findings reveal the role of vtRNA1-1 in ensuring intracellular catabolic compartment stability and functionality, suggesting its importance in lysosome-mediated chemotherapy resistance.

scholarly journals circATP2A2 promotes osteosarcoma progression by upregulating MYH9

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1749-1761
Author(s):  
Xin Cao ◽  
Xianfeng Meng ◽  
Peng Fu ◽  
Lin Wu ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Area Under Curve ◽  
Prognostic Biomarker ◽  
Migration And Invasion ◽  
Promising Target ◽  
Repressive Effect ◽  
Cell Malignancy

Abstract Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro. circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment.

scholarly journals KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jing Chen ◽  
Cui-Cui Zhao ◽  
Fei-Ran Chen ◽  
Guo-Wei Feng ◽  
Fei Luo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

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