P8 KERATIN 17 PROMOTES CELLS PROLIFERATION AND METASTASIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Liu Zhun ◽  
Shen Zhimin ◽  
Zhang Peipei ◽  
Yu Shaobin ◽  
Gao Lei ◽  
...  
Keyword(s):  
Wound Healing ◽  
Colony Formation ◽  
Prognostic Significance ◽  
Migration And Invasion ◽  
Migration Ability ◽  
Chamber Experiment ◽  
Proliferation And Metastasis ◽  
The Impact

Abstract Background Keratin17(KRT17), as a multifunction cytoskeletal protein, associated with a multitudinous of biological processes, including cell proliferation, migration, and invasion. Previously, we have found up-expression of KRT17 genes in ESCC tissues. Currently, published kinds of researches claimed KRT17 is engaged in the tumorigenesis and progression of multiple cancers. However, the prognostic significance of KRT17 in ESCC patients and its effects in ESCC progression remains indistinct. Methods We verified the expression level of KRT17 in ESCC tissues by Western blotting and q-PCR and constructed KRT17 upregulated and knockdown EC9706 and Eca109 cells by Lentivirus overexpression and CAS9. The function of KRT17 in ESCC proliferation and metastasis were studied in vitro. We performed CCK-8 assays and plate colony formation assays and the plate colony formation assays to explore the effect of KRT17 on the proliferation, Moreover, the trans-well migration chamber experiment and wound healing test was taken to reveal the impact of KRT17 on migration capabilities. Results We verified that KRT17 is overexpressed in ESCC tissues and the role of KRT17 in the malignant behavior of ESCC in vitro and vivo . In CCK-8 assays and plate colony formation assays. We conformed proliferation capacity was notably enhanced by overexpression of KRT17 but compromised when KRT17 was knocked out. On the other hand, we used the plate colony formation assays to explore the effect of KRT17 on the proliferation of ESCC cells. KRT17 up-regulated significantly strengthened the proliferation while the KRT17 knockdown was weakened. To reveal the impact of KRT17 on migration, the trans-well migration chamber experiment was used to compare the role of down-regulation and up-regulation of KRT17 in migration; the results demonstrated that reducing expression of KRT17 significantly blocked the movement of ESCC cells as compared with the empty vector control. Otherwise, it has been confirmed that the cell migration ability employs a wound healing/scratch test because wound closure is generally a measure of cell motility. The results showed KRT17 overexpression notably reinforced the mobility of ESCC cells compared with the empty groups, whereas KRT17 knockdown cells prolonged the time to close the injury compared to blank groups. Collectively, these discoveries support that the increased expression of KRT17 in ESCC cells promoted a more proliferation and migratory phenotype in vitro. Conclusion The breakthrough indicated that the up-regulation of KRT17 in ESCC is closely related to malignant progression. Our data confirmed that KRT17 plays an essential role in reinforcing proliferation and metastasis in ESCC. Thence, KRT17 may serve as a significant molecular target for the diagnosis and therapy of ESCC.

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 Integrated Bioinformatics Data Analysis and Experimental Studies Reveals Prognostic Significance of ALDH Family in Endometria Cancer

2021 ◽  
Author(s):  
Zhou-Tong Dai ◽  
Yuan Xiang ◽  
Xing-Hua Liao
Keyword(s):  
Cell Lines ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Experimental Studies ◽  
Female Reproductive Tract ◽  
The Body ◽  
Mouse Tumor ◽  
The Impact

Abstract Background Uterine Corpus Endometrial Cancer (UCEC) is one of the three common malignant tumors of the female reproductive tract. According to reports, the cure rate of early UCEC can reach 95%. Therefore, the development of prognostic markers will help UCEC patients to find the disease earlier and develop treatment earlier. The ALDH family was first discovered to be the essential gene of the ethanol metabolism pathway in the body. Recent studies have shown that ALDH can participate in the regulation of cancer. Methods We used the gene profile data of 33 cancers in the TCGA database to analyze the expression and survival of the ALDH family. GO, KEGG, PPI multiple functional analysis was used to predict the regulatory role of ALDH family in cancer. In addition, using CCK-8, colony formation, nude mouse tumor formation and other methods, the in vitro function of UCEC cancer cell lines was tested to further confirm the key role of ALDH2 expression in the proliferation of UCEC cell lines. Finally, Lasso and Cox regression methods were used to establish an overall survival prognosis model based on ALDH2 expression. Result In our research, we explored the expression of ALDH family in 33 cancers. It was found that ALDH2 was abnormally expressed in UCEC. Besides, in vivo and in vitro experiments were conducted to explore the effect of ALDH2 expression on the proliferation of UCEC cell lines. Meanwhile, the change of its expression is not due to gene mutations, but is regulated by miR-135-3p. At the same time, the impact of ALDH2 changes on the survival of UCEC patients is deeply discussed. Finally, a nomogram for predicting survival was constructed, with a C-index of 0.798 and AUC of 0.764. Conclusion This study suggests that ALDH2 may play a crucial role in UCEC progression and has the potential as a prognostic biomarker of UCEC.

scholarly journals The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Cao ◽  
Li Xu ◽  
Xiaohong Yang ◽  
Yuan Dong ◽  
Hongbin Luo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Cell Counting ◽  
Migration Ability ◽  
Cell Growth And Migration ◽  
Cell Based Therapy ◽  
And Migration ◽  
Proliferation And Migration

Background. Refractory wound healing is a severe complication of diabetes with a significant socioeconomic burden. Whereas current therapies are insufficient to accelerate repair, stem cell-based therapy is increasingly recognized as an alternative that improves healing outcomes. The aim of the present study is to explore the role of cycloastragenol (CAG), a naturally occurring compound in Astragali Radix, in ameliorating refractory cutaneous wound healing in vitro, which may provide a new insight into therapeutic strategy for diabetic wounds. Methods. Human epidermal stem cells (EpSCs) obtained from nine patients were exposed to CAG, with or without DKK1 (a Wnt signaling inhibitor). A lentiviral short hairpin RNA (shRNA) system was used to establish the telomerase reverse transcriptase (TERT) and β-catenin knockdown cell line. Cell counting kit-8, scratch wound healing, and transwell migration assay were used to determine the effects of CAG in cell growth and migration. The activation of TERT, β-catenin, and c-Myc was determined using real-time qPCR and western blot analysis. Chromatin immunoprecipitation (ChIP) was performed to evaluate the associations among CAG, TERT, and Wnt/β-catenin signals. Results. CAG not only promoted the proliferation and migration ability of EpSCs but also increased the expression levels of TERT, β-catenin, c-Myc. These effects of CAG were most pronounced at a dose of 0.3 μM. Notably, the CAG-promoted proliferative and migratory abilities of EpSCs were abrogated in TERT and β-catenin-silenced cells. In addition, the ChIP results strongly suggested that CAG-modulated TERT was closely associated with the activation of Wnt/β-catenin signaling. Conclusion. Our data indicate that CAG is a TERT activator of EpSCs and is associated with their proliferation and migration, a role it may play through the activation of Wnt/β-catenin signaling.

scholarly journals A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ye Feng ◽  
Ying Xu ◽  
Yongjian Gao ◽  
Yiying Chen ◽  
Xuefeng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Functional Relationships ◽  
Rna Immunoprecipitation ◽  
Proliferation And Metastasis

AbstractLong noncoding RNAs (lncRNAs) show emerging roles in colorectal cancer (CRC) development and are considered to be involved in the potential mechanism of tumor malignancy. While Sox2 overlapping transcript (SOX2OT) has been implicated in the progression of multiple cancers, its role in CRC remains to be explored. In this study, in situ hybridization (ISH) and qRT-PCR were performed to establish the functional relationships between SOX2OT and CRC deranged in CRC tissue and cells. Subsequently, SOX2OT shRNAs vectors were transfected into CRC cells to performed loss-of-function assays to detect the potential role of SOX2OT on proliferation and metastasis in vitro and vivo. The results showed SOX2OT was an oncogene that was up-regulated in human CRC tissues and cell lines. SOX2OT silencing suppressed cell proliferation, migration, and invasion in CRC cells in vitro, and inhibited tumorigenesis in the mouse xenografts. Bioinformatic predictive analysis coupled with the dual-luciferase reporter, RNA immunoprecipitation (RIP), and functional rescue assay elucidated the mechanistic network of the SOX2OT-miR-194-5p-SOX5 axis in CRC. Mechanistically, SOX2OT acted as a competing endogenous RNA (ceRNA) to upregulate SOX5 by sponging miR-194-5p. Downregulated SOX2OT boosted miR-194-5p expression, thus decreased the protein level of SOX5, which suppresses tumorgenesis of CRC.

scholarly journals BEL β-Trefoil Reduces the Migration Ability of RUNX2 Expressing Melanoma Cells in Xenotransplanted Zebrafish

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1270 ◽  
Author(s):  
Maria Teresa Valenti ◽  
Giulia Marchetto ◽  
Massimiliano Perduca ◽  
Natascia Tiso ◽  
Monica Mottes ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Migration And Invasion ◽  
In Vivo Model ◽  
Wild Mushroom ◽  
Migration Ability ◽  
Melanoma Patients ◽  
Annual Mortality

RUNX2, a master osteogenic transcript ion factor, is overexpressed in several cancer cells; in melanoma it promotes cells migration and invasion as well as neoangiogenesis. The annual mortality rates related to metastatic melanoma are high and novel agents are needed to improve melanoma patients’ survival. It has been shown that lectins specifically target malignant cells since they present the Thomsen–Friedenreich antigen. This disaccharide is hidden in normal cells, while it allows selective lectins binding in transformed cells. Recently, an edible lectin named BEL β-trefoil has been obtained from the wild mushroom Boletus edulis. Our previous study showed BEL β-trefoil effects on transcription factor RUNX2 downregulation as well as on the migration ability in melanoma cells treated in vitro. Therefore, to better understand the role of this lectin, we investigated the BEL β-trefoil effects in a zebrafish in vivo model, transplanted with human melanoma cells expressing RUNX2. Our data showed that BEL β-trefoil is able to spread in the tissues and to reduce the formation of metastases in melanoma xenotransplanted zebrafish. In conclusion, BEL β-trefoil can be considered an effective biomolecule to counteract melanoma disease.

scholarly journals Silencing of hsa_circ_0009035 suppresses cervicalprogression and enhances radiosensitivity through miR-889-3p-dependent regulation of HOXB7

2021 ◽  
Author(s):  
Xia Zhao ◽  
Weilei Dong ◽  
Guifang Luo ◽  
Jing Xie ◽  
Jie Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Colony Formation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
The Impact

Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, have been identified as critical regulators in human carcinogenesis. Here, we investigated the precise actions of hsa_circ_0009035 in the progression and radioresistance of cervical cancer (CC). The levels of hsa_circ_0009035, microRNA (miR)-889-3p and homeobox B7 (HOXB7) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease R (RNase R) and Actinomycin D assays were used to assess the stability of hsa_circ_0009035. Cell proliferation, cell cycle progression, apoptosis, migration and invasion were gauged by the Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, respectively. Cell colony formation and survival were determined by the colony formation assay. Targeted correlations among hsa_circ_0009035, miR-889-3p and HOXB7 were examined by the dual-luciferase reporter, RNA immunoprecipitation (RIP) or RNA pull-down assay. Animal studies were performed to evaluate the impact of hsa_circ_0009035 on tumor growth. We found that hsa_circ_0009035 was highly expressed in CC tissues and cells, and it was associated with the radioresistance of CC patients. Moreover, the silencing of hsa_circ_0009035 inhibited CC cell proliferation, migration, invasion, and enhanced apoptosis and radiosensitivity in vitro and weakened tumor growth in vivo. Mechanistically, hsa_circ_0009035 directly targeted miR-889-3p by binding to miR-889-3p, and hsa_circ_0009035 modulated HOXB7 expression through miR-889-3p. HOXB7 was a functional target of miR-889-3p in regulating CC progression and radioresistance in vitro, and hsa_circ_0009035 modulated CC progression and radioresistance in vitro by miR-889-3p. Our current study first identified hsa_circ_0009035 as an important regulation of CC progression and radioresistance at least in part through targeting the miR-889-3p/HOXB7 axis, highlighting its significance as a potential therapeutic target for CC treatment.

Use of co-expression of HGF and c-Met to predict peritoneal dissemination established by autocrine HGF/c-Met signaling in gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 40-40 ◽  
Author(s):  
Y. Toiyama ◽  
K. Tanaka ◽  
H. Yasuda ◽  
S. Saigusa ◽  
H. Fujikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peritoneal Dissemination ◽  
Biological Effects ◽  
Immunohistochemical Analysis ◽  
Migration And Invasion ◽  
Migration Ability ◽  
Epithelial Tumour

40 Background: Epithelial mesencymal transition (EMT) promotes facilitates migration and invasion of epithelial tumour cells. EMT is induced by growth factors implicated in theses process such as hepatocyte growth factor (HGF). Our aim of this study is whether HGF/c-Met pathway is associated with metastasis of gastric cancer (GC), especially in peritoneal dissemination (PD). Methods: HGF and c-Met expression and EMT related molecules were evaluated using real-time PCR and immunohistochemistry in GC tissues. The role of HGF/c-Met pathway for EMT and anoikis was determined and c-Met TKI (SU11274) was tested for their ability to block HGF-induced biological effects in vitro and vivo. Results: In HGF(-)c-Met(+) GC cells,recombinant HGF promoted EMT phenotype characterized by morphology, impaired E-cadherin and induction of Vimentin. HGF promoted cell growth, invasiveness, migration ability and inhibition of anoikis. SU11274 blocked HGF-induced EMT and the biological effects in vitro. In contrast of HGF(+)c-Met(+) GC cells, HGF exposure was not affected biological outcome of EMT and anoikis but SU11274 blocked biological effect as same as in HGF(-)c-Met(+) GC cells. In vivo, HGF(+)c-Met(+) GC cell line only established PD and SU11274 intraperitoneally caused an inhibition of PD growth. Clinically, HGF expression was significantly positive correlated with c-Met expression in GC specimens. Increased HGF and c-Met demonstrated a significantly associated with poor prognosis and can predict PD, respectively. Furthermore, HGF was one of the independent factors for predicting PD. Immunohistochemical analysis showed HGF and c-Met were predominantly co-expressed in cancer cell of both primary GC and PD. Conclusions: We have demonstrated that HGF/c-Met pathway as an inducer of EMT and anoikis inhibition in GC cell. Co-expression of HGF and c-Met implicates its potential to promote PD in GC. Blocking the autocrine HGF/c-Met pathway may be clinically useful for the treatment of PD in GC. No significant financial relationships to disclose.

P11 KRT17 PROMOTES PROLIFERATION AND METASTASIS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA LEADING TO POOR PROGNOSIS

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Liu Zhun ◽  
Shen Zhimin ◽  
Zhang Peipei ◽  
Yu Shaobin ◽  
Gao Lei ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Prognostic Significance ◽  
Predictive Biomarker ◽  
Vital Role ◽  
Migration And Invasion ◽  
Depth Of Invasion ◽  
Node Metastasis ◽  
Proliferation And Metastasis ◽  
Migration Capacity

Abstract Background Keratin17(KRT17), as a multifunction cytoskeletal protein, associated with a multitudinous of biological processes, including cell proliferation, migration, and invasion. Previously, we have found overexpression of KRT17 genes in ESCC tissues. Currently, published kinds of researches claimed KRT17 is engaged in the tumorigenesis and progression of multiple cancers. However, the prognostic significance of KRT17 in ESCC patients and its effects in ESCC progression remain indistinct. Methods We verified the expression of KRT17 in ESCC tissues by Western blotting and q-PCR. And then the immunochemistry was performed to investigate the KRT17 expression in 64 ESCC tissue specimens. KRT17 upregulated, and knockdown EC9706 and Eca109 cells were constructed by Lentivirus overexpression and CRISPR-Cas9. The function of KRT17 in ESCC proliferation and metastasis were studied by CCK-8 assays, plate colony formation assays, trans-well and wound healing in vitro. Results overexpression of KRT17 was verified in 12 pairs of fresh ESCC tissues. We found that the expression of KRT17 was remarkably positively correlated with the depth of invasion (T) (P<0.05), lymph node metastasis (N) (P<0.05), tumor node metastasis (TNM) stage (P<0.0001). High expression of KRT17 predicted a lower 5-year survival rate(P<0.001) of ESCC patients. We verified the KRT17 malignant behavior of ESCC in vitro. We conformed proliferation and migration capacity of ESCC were significantly enhanced by overexpression of KRT17 but compromised when KRT17 was knocked down. Collectively, it supported that the increased expression of KRT17 promoted proliferation and migratory phenotype of ESCC. Conclusion The breakthrough indicated that the upregulation of KRT17 in ESCC is closely related to malignant progression, our findings revealed that KRT17 plays a vital role in facilitating proliferation and metastasis, and could be used as a novel predictive biomarker, thus providing a novel diagnosis and therapeutic target for ESCC patients. Keywords: Molecular target ESCC Keratin17 Therapeutic target

scholarly journals Potential Role of SWI/SNF Complex Subunit Actin-Like Protein 6A in Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingying Wang ◽  
Zuozeng Cao ◽  
Yingze Wei ◽  
Jiawen Zhang ◽  
Zhongping Cheng
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Colony Formation ◽  
Gene Set Enrichment Analysis ◽  
Migration And Invasion ◽  
Cancer Type

SWI/SNF complex subunit Actin-like protein 6A (ACTL6A) has been regarded as an oncogene, regulating the proliferation, migration and invasion of cancer cells. However, the expression pattern and biological role of ACTL6A in cervical cancer have not been reported. In this study, the mRNA expression and protein level of ACTL6A in cervical cancer samples were determined by public database and immunohistochemical (IHC) analysis. The effects of ACTL6A on cervical cancer cells were investigated via MTT, colony-formation assay, tumor xenografts and flow cytometry. Gene set enrichment analysis (GSEA) was used to explore the potential mechanism of ACTL6A in regulating tumorigenesis of cervical cancer. The results revealed that ACTL6A was markedly upregulated in cervical cancer tissues. Silencing ACTL6A expression resulted in decreased cervical cancer cell proliferation, colony formation and tumorigenesis in vitro and in vivo. Furthermore, we demonstrated that knockdown of ACTL6A induced cell cycle arrest at G1 phase, ACTL6A-mediated proliferation and cell cycle progression were c-Myc dependent. Our study provides the role of ACTL6A in cervical oncogenesis and reveals a potential target for therapeutic intervention in this cancer type.

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.

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