Endogenous Melatonin Concentration Along With the Expression of Mitochondrial Regulator Genes Is Elevated by the Serum Shock Process in the U87-MG Cell Line

Abstract Glioblastoma, also known as the fourth grade in the development of astrocytoma according to the World Health Organization, is a tumor in the glial region confined to the central nervous system with high invasion capability to the parenchyma of the brain. Recent findings suggest that melatonin can be synthesized outside the pineal gland tissue. Mitochondria can produce melatonin independently but in coordination with cell demands which plays a critical role in regulating the cell cycle and cell metabolism. hence, we aimed to examine the relationship between cell metabolism and the induction of endogenous melatonin increase induced by the serum shock process, then, determine the percentage of cell proliferation.Background: glioblastoma is a highly invasive tumor of glial cell of brain tissue. Recently it was reported that melatonin can be produced in mitochondria organelle of the glioblastoma cells independent to pineal gland. Regarding the physiological function of melatonin released from pineal gland in regulation of rhythmicity, here we aimed to investigate if serum shock standard protocol known for cellular rhythm regulator can change the melatonin production ability of the glioblastoma cell.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PGC-1α, and DRP1 were measured, using qRT-PCR method.Results: our findings showed increased (two times) concentration of cellular and released endogenous melatonin in the FBS shock treated U87-MG glioblastoma cells compared to the control group. we found significant up-regulation of the mitochondria or circadian regulator genes (TFAM, BMAL1, PGC-1α, and DRP1) at mRNA level; in the FBS shock group compared to the control group (P <0.0002). Moreover, the percent of proliferative cell (Brdu positive) was also elevated in FBS shock group however it was not statistically significant. Conclusion: the serum shock process has a far effect on the cellular behavior of the U87-MG cell line. regard to the results of the study, it is worth mentioning that an increase in the concentration of endogenous melatonin affects many signaling pathways within the U87-MG cell line, and the elevated expression of the candidate genes was the proof of this fact.by considering the results of this study it also should be noted that detailed investigating the role of endogenous melatonin and its effects on cancer cells is pivotal and by comparing the results of the normal cells with cancer cells we can find the hotspots of the involved signaling pathways that could help better understanding the biology of glioblastoma.

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“Endogenous Melatonin Concentration Along with the Expression of Mitochondrial Regulator Genes is Elevated by the Serum Shock Process in the U87-MG Cell Line”

10.21203/rs.3.rs-881036/v2 ◽

2022 ◽

Author(s):

Shayan Balkhi ◽

Marie Saghaeian Jazi ◽

Nader Mansour Samaei ◽

Mahtab Farahmandrad

Keyword(s):

Cell Proliferation ◽

Pineal Gland ◽

Shock Group ◽

Control Group ◽

Glioblastoma Cells ◽

Melatonin Concentration ◽

Shock Process ◽

Regulator Genes ◽

New Research ◽

Endogenous Melatonin

Abstract According to the World Health Organization, glioblastoma, also known as the fourth grade in the development of astrocytoma, is a glial tumor limited to the central nervous system with a strong ability to invade the brain parenchyma. Melatonin can be generated outside of the pineal gland tissue, according to new research. Melatonin is produced by mitochondria independently but in concert with cell demands, and it plays an important function in cell cycle and metabolism regulation. As a result, we set out to investigate the association between cell metabolism and the serum shock-induced increase in endogenous melatonin, as well as the percentage of cell proliferation.Background: Melatonin can be produced in the mitochondria organelle of glioblastoma cells without the involvement of the pineal gland, according to new research. Regarding the physiological function of melatonin secreted by the pineal gland in the regulation of rhythmicity, the goal of this study was to see if the glioblastoma cell's melatonin production ability could be influenced using a typical serum shock technique established for cellular rhythm regulator.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PPARGC1A(PGC1-α), and DNM1L(DRP1) were measured, using qRT-PCR method.Results: In comparison to the control group, serum shock treated U87-MG glioblastoma cells had higher concentrations of cellular and released endogenous melatonin (two times). At the mRNA level, we discovered considerable upregulation of mitochondrial or circadian regulator genes (TFAM, BMAL1, PPARGC1A, and DNM1L); in the shock group compared to the control group (P <0.0002). Furthermore, although the percentage of proliferative cells (Brdu positive) was higher in the shock group, it was not statistically significant.Conclusion: The serum shock procedure has a significant impact on the U87-MG cell line's cellular activity. In terms of the study's findings, it's worth noting that an increase in endogenous melatonin concentration influences several signaling pathways within the U87-MG cell line, as seen by the increased expression of candidate genes.In light of the findings of this study, it's worth noting that further research into the role of endogenous melatonin and its effects on cancer cells is critical, and that comparing the results of normal and cancer cells can reveal the hotspots of the signaling pathways involved, which could facilitate in better understanding the biology of glioblastoma.

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Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽

10.1093/qjmed/hcab088.011 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Rowaida Mohammed Reda M. M Aboushahba ◽

Fayda Ibrahim Abdel Motaleb ◽

Ahmed Abdel Aziz Abou-Zeid ◽

Enas Samir Nabil ◽

Dalia Abdel-Wahab Mohamed ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Wnt Signaling ◽

Cell Line ◽

Signaling Pathway ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Wnt Signaling Pathway ◽

Control Group ◽

Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

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Assessment of Anti-Ageing Potential of Consciousness Energy Healing Treated DMEM and HFF-1 Cells using Cellular Proliferation and Collagen Metabolism Assays

Lettters in Health & Biological Sciences ◽

10.15436/2475-6245.19.1977 ◽

2019 ◽

Vol 4 (1) ◽

pp. 1-6

Author(s):

Mahendra Kumar Trivedi ◽

Dahryn Trivedi ◽

Alice Branton ◽

Gopal Nayak ◽

Sambhu Charan Mondal ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Line ◽

Cellular Proliferation ◽

Negative Control Group ◽

Skin Aging ◽

Negative Control ◽

Control Group ◽

Complex Biological Process ◽

Collagen Level ◽

Energy Healing

Skin health and aging are the complex biological process influenced by several intrinsic (or endogenous) and extrinsic (or exogenous) factors. Various skin-based therapies are currently available to rejuvenate the skin, but they might be related with some side-effects such as scarring. The objective of the present study was to evaluate the effect of Consciousness Energy Healing Treatment (The Trivedi Effect®) on the human foreskin fibroblast (HFF-1) cell line and Dulbecco’s Modified Eagle Medium (DMEM) for skin health parameters like cell proliferation and synthesis of collagen. The rate of cellular proliferation in HFF-1 cells was identified, and the results found that the Biofield Energy Treated DMEM significantly (p ≤ 0.001) increased by 152.38% compared to the negative control group. Additionally, the cell proliferation was also significantly increased by 71.43% in the Biofield Energy Treated cells compared to the negative control group. Similarly, the collagen level was significantly (p ≤ 0.001) increased by 60.42% in the Biofield Energy Treated DMEM compared with the negative control group. Hence, the results exhibited a significant improvement of collagen synthesis and cellular proliferation in the Biofield Energy Treated DMEM for improving skin health. It can be concluded that The Trivedi Effect® - Consciousness Energy Healing Treatment might be a complementary and alternative approach with respect to the skin health, anti-aging in DMEM compared with the HFF-1 cell line. Therefore, the Biofield Energy Treated DMEM could be useful for the development of effective cosmetic products for the prevention and treatment of several skin problems such as erythema, contact dermatitis, skin aging, wrinkles, etc.

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Metformin suppresses the proliferation and invasion through NF-kB and MMPs in MCF-7 cell line

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0197 ◽

2019 ◽

Vol 45 (3) ◽

pp. 295-304

Author(s):

Nail Besli ◽

Guven Yenmis ◽

Matem Tunçdemir ◽

Elif Yaprak Sarac ◽

Sibel Doğan ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Line ◽

Cancer Cell Line ◽

Immunocytochemical Staining ◽

Breast Adenocarcinoma ◽

Control Group ◽

Expression Levels ◽

Er Positive ◽

Mcf 7

AbstractObjectiveMCF-7 cells, a breast cancer cell line, are used for experiments of estrogen receptor (ER)-positive breast cancer and many sub-clones representing different classes of ER-positive tumors. We aimed to determine the efficacy of metformin, a potential anti-cancer agent, on the cell proliferation, and the expressions of NF-kB (p65), MMP-2 and MMP-9 in MCF-7 cell line.Materials and methodsMCF-7 cells (human breast adenocarcinoma) were treated with elevating doses of metformin (0–50 mM) for 24 h. The anti-proliferative effect of metformin was studied by BrdU proliferation assay, and the expression levels of NF-kB (p65), MMP-2 and MMP-9 were analyzed by immunocytochemical staining.ResultsThe percentage of cell proliferation was reduced significantly by 10 and 50 mM doses of metformin (p < 0.001). The expression levels of nuclear NF-kB (p65), MMP-9 and MMP-2 were considerably reduced in 50 mM metformin treated cells while the expression of cytoplasmic NF-kB (p65) elevated compared to control group (p < 0.05). Ten millimolar metformin also reduced expression of MMP-9 significantly (p < 0.05).ConclusionMetformin may act on the proliferation, and the processes of invasion and metastasis of MCF-7 cells through blocking NF-kB, which is intensely expressed in breast cancer cells, and through diminishing the expression of MMP-2 and MMP-9 significantly.

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Artesunate Decreases β-Catenin Expression, Cell Proliferation and Apoptosis Resistance in the MG-63 Human Osteosarcoma Cell Line

Cellular Physiology and Biochemistry ◽

10.1159/000484118 ◽

2017 ◽

Vol 43 (5) ◽

pp. 1939-1949 ◽

Cited By ~ 4

Author(s):

Peng Chen ◽

Wan-Li Gu ◽

Ming-Zhi Gong ◽

Jun Wang ◽

Dong-Qing Li

Keyword(s):

Cell Proliferation ◽

Cell Line ◽

Western Blotting ◽

Mtt Assay ◽

Control Group ◽

Osteosarcoma Cell ◽

Human Osteosarcoma Cell Line ◽

Expression Levels ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cell

Background: This study aims to determine the effects of artesunate on proliferation, apoptosis and β-catenin expression in the human osteosarcoma cell line MG-63. Methods: MG-63 cells in the logarithmic growth phase were collected and cultured with different concentrations of artesunate (12.5 µg/mL, 25 µg/mL and 50 µg/mL) for 24 h, 48 h and 72 h. The total number of MG-63 cells and the morphological changes were observed under an inverted microscope. The MTT assay was adopted to test the inhibition rate (IR) of cell growth. The apoptosis rate was detected using annexin V/propidium iodide (PI) staining. Cell cycle distribution was identified by flow cytometry (FCM), and the expression levels of β-catenin, cyclins and cyclin dependent kinases (CDKs) were measured using Western blotting. Results: The results of the MTT assay indicated that artesunate could remarkably inhibit MG-63 cell proliferation compared with the rates in the untreated control group (0 µg/mL artesunate), and the inhibitory effect was dose-dependent. The apoptosis rate of MG-63 cells was elevated as the concentration of artesunate increased, and all the rates were significantly higher than that in the control group. Additionally, as the artesunate concentration increased, the proportion of MG-63 cells in G0/G1 phase gradually declined whereas that of cells in the G2/M and S phases increased. Western blotting confirmed that a higher concentration of artesunate reduced the expression levels of β-catenin, cyclin A, cyclin D1 and CDK1 and increased the expression levels of cyclin B1; however, artesunate had no impact on CDK2 expression in MG-63 cells. Conclusion: These results demonstrated that artesunate can inhibit β-catenin expression and cell proliferation as well as promote cell apoptosis in MG-63 cells, which indicates that artesunate may serve as a promising drug in the clinical treatment of osteosarcoma.

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Carboxypeptidase E down-regulation regulates transcriptional and epigenetic profiles in pancreatic cancer cell line: A network analysis

Cancer Biomarkers ◽

10.3233/cbm-191163 ◽

2020 ◽

Vol 29 (1) ◽

pp. 79-88

Author(s):

Zhile Bai ◽

Mengyu Feng ◽

Yang Du ◽

Lin Cong ◽

Yong Cheng

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Network Analysis ◽

Cell Line ◽

Signaling Pathway ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Differentially Expressed ◽

Control Group ◽

Down Regulation

BACKGROUND: Pancreatic cancer is a malignant tumor and its incidence has increased in recent years. Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme that has been shown to be associated with tumor growth and invasion in various cancers including pancreatic cancer. OBJECTIVE: To understand the molecular mechanism underlying the proliferative effects of CPE in cancer cells. METHODS: We down-regulated CPE gene expression in PANC-1 cell, a pancreatic cell line, and investigated mRNA, miRNA, circRNA and lncRNA expression profiling in PANC-1 cells from control group and CPE knock-down group by microarray analysis. We further validated the top 14 differentially expressed circRNAs by qRT-PCR. RESULTS: Our results showed that CPE down-regulation caused decreased cell proliferation. The microarray data showed 107, 15, 299 and 360 differentially expressed mRNAs, miRNAs, circRNAs, and lncRNAs, respectively between control group and CPE knock-down group. Of Which, 41 mRNAs, 12 miRNAs, 133 circRNAs, and 262 lncRNAs were down-regulated; 66 mRNAs, 3 miRNAs, 166 circRNAs, and 98 lncRNAs were up-regulated. Bioinformatics analysis showed that the top significantly enriched pathways for the differentially expressed RNAs were related to cancer onset and/or progression, these included p53 signaling pathway, ECM-receptor interaction, focal adhesion and Wnt signaling pathway. We further performed network analysis to assess the mRNA, miRNA, circRNA and lncRNA correlations, and showed that HUWE1, hsa-miR-6780b-5p, has_circ_0058208 and lnc-G3BP1-3:8 were in the core position of the network. CONCLUSIONS: Taken together, these results identified potential CPE regulated core genes and pathways for cell proliferation in pancreatic cancer cell, and therefore provide potential targets for the treatment of pancreatic cancer.

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lncRNA-GPAND Promotes Gastric Cancer Progression via RUNX2 and MMP13

10.21203/rs.3.rs-1061004/v1 ◽

2021 ◽

Author(s):

Ying Wang ◽

Xiaojuan Pei ◽

Chunbing Wang ◽

Zhibo Tan

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cell Line ◽

Cell Lines ◽

Molecular Mechanisms ◽

Tissue Array ◽

Control Group ◽

Cancer Tissue ◽

Expression Levels ◽

Ags Cell Line

Abstract Background: Gastric cancer (GC) is still one major reason for cancer-related death worldwide and in China, which ranks the second highest common cancer death rate. It is of great importance to study the molecular mechanisms by which gastric cancer develops. Methods: In this study, in situ hybridization histochemistry (ISHH) was used to examine the lncRNA-GPAND expression levels using gastric cancer tissue array. The real-time live-cell imaging system was used to investigate the effect of GPAND on cell proliferation and apoptosis of GC cell lines. Cell cycle of AGS cell line was examined after GPAND was suppressed using the flow cytometry (FCM). Transwell method was used to study the effect of GPAND on the invasion characteristics of GC cell line. Then the next generation sequencing (NGS) was used to study the potential molecular mechanism and the pathway, and the RT-qPCR was performed to verify the potential targets found by NGS method. Results: It was shown that GPAND was significantly over-expressed in the gastric cancer (GC) tissues (n=215) compared with the paired non-cancerous tissues (n=215), the expression levels of GPAND of GC tissues of TNM stage I-II (n=45) were significantly higher than that of stage III-IV (n=147). It has shown that knockdown of GPAND inhibited the AGS and N87 cell proliferation and promoted the cell apoptosis of AGS and N87 cell lines significantly, and the G1 phase percentage was remarkably increased in GPAND knockdown group of AGS cell line compared with control group. Moreover, suppression of GPAND inhibited the AGS cell invasion significantly. It was found via the NGS method that RUNX2 and MMP13 were significantly up-regulated when the GPAND was over-expressed. Conclusions: These observations suggest the lncRNA-GPAND/RUNX2/MMP13 axis to be a viable therapeutic target for gastric cancer.

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METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

Acta Endocrinologica ◽

10.1530/acta.0.0690165 ◽

1972 ◽

Vol 69 (1) ◽

pp. 165-173 ◽

Cited By ~ 9

Author(s):

H. Schmidt ◽

I. Noack ◽

K. D. Voigt

Keyword(s):

Cell Proliferation ◽

Cell Metabolism ◽

Seminal Vesicles ◽

Male Rats ◽

Ventral Prostate ◽

Nucleic Acid Content ◽

The Difference ◽

Independent Effects ◽

Sites Of Action ◽

Peripheral Metabolism

ABSTRACT The effect of testosterone and 5α-dihydrotestosterone on protein and nucleic acid content as well as on the activities of some enzymes has been studied in the ventral prostate and the seminal vesicles of immature castrated rats. Both androgens were given intraperitoneally in doses of 1 mg daily for one or three days the rats were sacrificed one day after the last injection. In the prostate it was found that 5α-dihydrotestosterone had a greater effect on DNA increase, i. e. cell proliferation than testosterone, whereas cell metabolism was stimulated by the two androgens to nearly the same extent. In the seminal vesicles a single dose led to the same results as had been obtained in the prostate, i. e. a greater cell proliferative action of 5α-dihydrotestosterone and an equal stimulation of cell metabolism by testosterone and 5α-dihydrotestosterone was also observed. When three doses of the two androgens were given, cell proliferation as well as cell metabolism in the seminal vesicles were significantly more increased after 5α-dihydrotestosterone than after testosterone. The difference of action after systemic administration of the two androgens is explained by their different accumulation and by their different peripheral metabolism in the target tissues. From the partly independent effects of various androgens on cell proliferation and cell metabolism the conclusion may be drawn that there exist at least two intracellular sites of action.

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Effects of Papaya Leaf Extract (Carica papaya L.) on Cellular Proliferation and Apoptosis in Cervical Cancer Mice Model

Phytothérapie ◽

10.3166/phyto-2018-0096 ◽

2019 ◽

Vol 17 (5) ◽

pp. 265-275

Author(s):

Y. Peristiowati ◽

Y. Puspitasari ◽

Indasah

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Hela Cells ◽

Leaf Extract ◽

Caspase 3 ◽

Methanol Extract ◽

Negative Control ◽

Proliferation Index ◽

Control Group ◽

P53 Expression

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.

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HIF1A is Overexpressed in Medulloblastoma and its Inhibition Reduces Proliferation and Increases EPAS1 and ATG16L1 Methylation

Current Cancer Drug Targets ◽

10.2174/1568009617666170315162525 ◽

2018 ◽

Vol 18 (3) ◽

pp. 287-294 ◽

Cited By ~ 8

Author(s):

Gustavo Alencastro Veiga Cruzeiro ◽

Maristella Bergamo dos Reis ◽

Vanessa Silva Silveira ◽

Regia Caroline Peixoto Lira ◽

Carlos Gilberto Carlotti Jr ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Line ◽

Cellular Proliferation ◽

Mrna Level ◽

Relevant Information ◽

Protein Stabilization ◽

Mrna Levels ◽

Medulloblastoma Cell Line ◽

Pediatric Medulloblastoma ◽

Fresh Frozen

Background: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxiarelated genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions. Objective: Our study focused on evaluation the of CA9, CA12, HIF1A, EPAS1, SCL2A1 and VEGF genes in 41 pediatric fresh-frozen medulloblastoma sample. Additionally, we analyzed the effect of hypoxia and normoxia in the pediatric medulloblastoma cell-line UW402. Furthermore, we assessed the effects of HIF1A knockdown in cell-proliferation and methylation levels of genes related to hypoxia, apoptosis and autophagy. Method: qPCR was performed to evaluate mRNA levels, and Western blot to confirm HIF1A silencing in both patient samples and cell line. Pyrosequencing was performed to asses the methylation levels after HIF1A knockdown in the UW402 cell line. Results: A higher HIF1A mRNA level was observed in MB patients when compared to the cerebellum (non-tumor match). In UW402 MB cell-line, chemically induced hypoxic resulted in an increase of mRNA levels of HIF1A, VEGF, SCL2A1 and CA9 genes. Additionally, HIF1A knockdown induced a decrease in the expression of hypoxia related genes and a decrease of 30% in cell proliferation was also observed. Also, a significant increase in the methylation of ATG16L1 promoter and decrease in the methylation of EPAS1 promoter were observed after HIF1A knockdown. Conclusion: HIF1A knockdown in medulloblastoma cells lead to decreased cellular proliferation, suggesting that HIF1A can be a potential therapeutic target to be explored in the medulloblastoma. However, the mechanisms behind HIF1A protein stabilization and function are very complex and more data need to be generated to potentially use HIF1A as a therapeutical target.

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