scholarly journals Increased activation of HDAC1/2/6 and Sp1 underlies therapeutic resistance and tumor growth in glioblastoma

2020 ◽  
Vol 22 (10) ◽  
pp. 1439-1451
Author(s):  
Wen-Bin Yang ◽  
Che-Chia Hsu ◽  
Tsung-I Hsu ◽  
Jing-Ping Liou ◽  
Kwang-Yu Chang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Target Genes ◽  
Integration Site ◽  
Recurrent Glioblastoma ◽  
Stem Cell Population ◽  
Therapeutic Resistance ◽  
Low Grade ◽  
Human Telomerase Reverse Transcriptase ◽  
Resistant Cells

Abstract Background Glioblastoma is associated with poor prognosis and high mortality. Although the use of first-line temozolomide can reduce tumor growth, therapy-induced stress drives stem cells out of quiescence, leading to chemoresistance and glioblastoma recurrence. The specificity protein 1 (Sp1) transcription factor is known to protect glioblastoma cells against temozolomide; however, how tumor cells hijack this factor to gain resistance to therapy is not known. Methods Sp1 acetylation in temozolomide-resistant cells and stemlike tumorspheres was analyzed by immunoprecipitation and immunoblotting experiments. Effects of the histone deacetylase (HDAC)/Sp1 axis on malignant growth were examined using cell proliferation–related assays and in vivo experiments. Furthermore, integrative analysis of gene expression with chromatin immunoprecipitation sequencing and the recurrent glioblastoma omics data were also used to further determine the target genes of the HDAC/Sp1 axis. Results We identified Sp1 as a novel substrate of HDAC6, and observed that the HDAC1/2/6/Sp1 pathway promotes self-renewal of malignancy by upregulating B cell-specific Mo-MLV integration site 1 (BMI1) and human telomerase reverse transcriptase (hTERT), as well as by regulating G2/M progression and DNA repair via alteration of the transcription of various genes. Importantly, HDAC1/2/6/Sp1 activation is associated with poor clinical outcome in both glioblastoma and low-grade gliomas. However, treatment with azaindolyl sulfonamide, a potent HDAC6 inhibitor with partial efficacy against HDAC1/2, induced G2/M arrest and senescence in both temozolomide-resistant cells and stemlike tumorspheres. Conclusion Our study uncovers a previously unknown regulatory mechanism in which the HDAC6/Sp1 axis induces cell division and maintains the stem cell population to fuel tumor growth and therapeutic resistance.

scholarly journals Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11591
Author(s):  
Jianfeng Guo ◽  
Yapei Zhu ◽  
Lili Yu ◽  
Yuan Li ◽  
Jing Guo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Epithelial Ovarian Cancer ◽  
Target Genes ◽  
Tumor Growth Inhibition ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
P53 Target Genes

Background Ovarian cancer is the most common gynecological malignancy and is difficult to manage due to the emergence of resistance to various chemotherapeutic drugs. New efforts are urgently awaited. Aspirin, which is traditionally considered a nonsteroidal anti-inflammatory drug (NSAID), has been reported to exert potential chemopreventive effects. Therefore, we aimed to investigate the anticancer effect and explore the underlying molecular mechanisms of aspirin on epithelial ovarian cancer (EOC) cells. Methods We conducted wound healing, transwell migration, EdU cell proliferation, colony formation and apoptosis detection assays to observe the effects of aspirin on the migration, proliferation and apoptosis of EOC cells (A2870, Caov-3, and SK-OV-3). EOC cells were treated with a combination of aspirin and cisplatin (CDDP) to observe the effect of aspirin on enhancing CDDP sensitivity. Orthotopic xenograft models of ovarian cancer established with A2780-Luciferase-GFP cells were applied to compare tumor growth inhibition in the control, CDDP and CDDP plus aspirin groups through in vivo imaging, which can be used to continuously monitor tumor growth. The expression and acetylation levels of p53 in EOC cells treated with aspirin were determined using western blotting, and p53 acetylation levels were examined in tumors harvested from the transplanted mice. Quantitative real-time PCR was used to assess the mRNA expression of p53 target genes. Results Aspirin inhibited migration and proliferation and induced apoptosis in EOC cell lines in a concentration-dependent manner. In vitro, aspirin enhanced the sensitivity of EOC cells to CDDP by increasing its inhibitory effect on proliferation and its effect on inducing apoptosis. In vivo, the differences in the tumor growth inhibition rates among the different CDDP experimental groups were statistically significant (p < 0.05). Aspirin did not affect p53 protein expression but increased the p53 acetylation level in a concentration-dependent manner. In addition, the mRNA levels of CDKN1A, BAX, FOXF1, PUMA, and RRAD in EOC cells were significantly increased by the aspirin treatment. Conclusions Aspirin inhibits tumor progression and enhances the CDDP sensitivity of EOC cells. These antitumor effects of aspirin might be mediated by p53 acetylation and subsequent activation of p53 target genes.

scholarly journals LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Bo Cheng ◽  
Aimei Rong ◽  
Quanbo Zhou ◽  
Wenlu Li
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Target Genes ◽  
Erk Signaling ◽  
Biological Functions ◽  
Colon Cells ◽  
Invasion And Migration

Abstract Background LncRNA LINC00662 is closely related to the occurrence and development of cancer. This study aims to explore the effect of LINC00662 on colon cancer tumor growth and metastasis and its molecular mechanism. Methods CCK8, colony formation, transwell, scratch wound, TUNEL, flow cytometry, RT-PCR, western blotting and immunohistochemistry assays were used to detect the proliferation, apoptosis, invasion and migration of colon cancer cell and mRNA and protein expressions. Luciferase reporter and RNA pull down assays were used to detect the combination of LINC00662 and miR-340-5p or IL22 and the combination of miR-340-5p and CLDN8/IL22. Co-immunoprecipitation were used to detect the co-expression of CLDN8 and IL22 in colon cell lines. The targets of LINC00662 were predicated by Starbase v2.0. The target genes of miR-340-5p were predicated by miRDB and TargetScan. GO and KEGG enrichment analysis were performed by DAVID website. Results LINC00662 was up-regulation in colon cancer tissues and cell lines. Univariate Cox regression analysis showed that the LINC00662 expression level was related to the poor prognosis. LINC00662-WT and miR-340-5p mimics co-transfection depressed luciferase activity and IL22/CLDN8-WT and miR-340-5p inhibitors co-transfection memorably motivated luciferase activity. LINC00662 overexpression promoted cell proliferation, invasion and migration, and inhibited cell apoptosis in colon cancer. In vivo xenograft studies in nude mice manifested that LINC00662 overexpression prominently accelerate tumor growth. There was an opposite reaction in the biological functions of colon cells and tumor growth between LINC00662 overexpression and LINC00662 inhibition in vitro and in vivo. The functions of miR-340-5p mimics regulating the biological functions of colon cells and tumor growth were consistent with those of LINC00662 inhibition. CLDN8 and IL22, as target genes of miR-340-5p, reversed the functions of LINC00662 affecting the biological functions of colon cells and the protein levels of Bax, Bcl-2, XIAP, VEGF, MMP-2, E-cadherin and N-cadherin. Co-immunoprecipitation experiments indicated that CLDN8 directly interact with IL22 in colon cell lines. LINC00662 regulated CLDN8 and IL22 expressions and the activation of ERK signaling pathway via targeting miR-340-5p. Conclusion LINC00662 overexpression promoted the occurrence and development of colon cancer by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway.

scholarly journals ASPP1 and ASPP2: Common Activators of p53 Family Members

2004 ◽  
Vol 24 (3) ◽  
pp. 1341-1350 ◽  
Author(s):  
Daniele Bergamaschi ◽  
Yardena Samuels ◽  
Boquan Jin ◽  
Sai Duraisingham ◽  
Tim Crook ◽  
...  
Keyword(s):  
Rna Interference ◽  
Tumor Growth ◽  
Target Genes ◽  
Family Members ◽  
Mutant P53 ◽  
P53 Family ◽  
P53 Target Genes

ABSTRACT We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53. We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA but not mdm2 or p21WAF-1/CIP1. The expression of ASPP1 and ASPP2 also enhances the apoptotic function of p63 and p73 by selectively inducing the expression of endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21WAF-1/CIP1. Removal of endogenous p63 or p73 with RNA interference demonstrated that (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common activators of all p53 family members. All these results suggest that ASPP1 and ASPP2 could suppress tumor growth even in tumors expressing mutant p53.

scholarly journals LNA-mediated anti–miR-155 silencing in low-grade B-cell lymphomas

Blood ◽  
2012 ◽  
Vol 120 (8) ◽  
pp. 1678-1686 ◽  
Author(s):  
Yong Zhang ◽  
Aldo M. Roccaro ◽  
Christopher Rombaoa ◽  
Ludmilla Flores ◽  
Susanna Obad ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Growth ◽  
B Cell ◽  
Stromal Cells ◽  
Leukemia Cell ◽  
Lymphocytic Leukemia ◽  
Locked Nucleic Acid ◽  
Low Grade ◽  
Seed Region

Abstract miR-155 acts as an oncogenic miR in B-cell lymphoproliferative disorders, including Waldenstrom macroglobulinemia (WM) and chronic lymphocytic leukemia, and is therefore a potential target for therapeutic intervention. However, efficient targeting of miRs in tumor cells in vivo remains a significant challenge for the development of miR-155–based therapeutics for the treatment of B-cell malignancies. In the present study, we show that an 8-mer locked nucleic acid anti–miR-155 oligonucleotide targeting the seed region of miR-155 inhibits WM and chronic lymphocytic leukemia cell proliferation in vitro. Moreover, anti–miR-155 delivered systemically showed uptake in the BM CD19+ cells of WM-engrafted mice, resulting in the up-regulation of several miR-155 target mRNAs in these cells, and decreased tumor growth significantly in vivo. We also found miR-155 levels to be elevated in stromal cells from WM patients compared with control samples. Interestingly, stromal cells from miR-155–knockout mice led to significant inhibition of WM tumor growth, indicating that miR-155 may also contribute to WM proliferation through BM microenvironmental cells. The results of the present study highlight the therapeutic potential of anti–miR-155–mediated inhibition of miR-155 in the treatment of WM.

scholarly journals MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct Suppression of JAG1/Notch1 Axis

2018 ◽  
Vol 50 (1) ◽  
pp. 261-276 ◽  
Author(s):  
Xiaobing Liu ◽  
Xing Luo ◽  
Yuqi Wu ◽  
Ding Xia ◽  
Wei Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Western Blot ◽  
Target Genes ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Qrt Pcr

Background/Aims: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. Methods: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. Results: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. Conclusion: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage.

scholarly journals RANKL/RANK Pathway and Its Inhibitor RANK-Fc in Uterine Leiomyoma Growth

2018 ◽  
Vol 103 (5) ◽  
pp. 1842-1849 ◽  
Author(s):  
Deborah E Ikhena ◽  
Shimeng Liu ◽  
Stacy Kujawa ◽  
Ecem Esencan ◽  
John S Coon ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cyclin D1 ◽  
Uterine Leiomyoma ◽  
Stem Cell Population ◽  
Intermediate Cell ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Gynecologic Tumor ◽  
Receptor Activator

Abstract Context Uterine leiomyomas are the most common type of gynecologic tumor in women. Objective To determine the role of the cytokine receptor activator of nuclear factor κ-Β ligand (RANKL); its receptor, receptor activator of nuclear factor κ-Β (RANK); and the RANKL/RANK pathway inhibitor RANK-Fc in leiomyoma growth. Design Messenger RNA (mRNA) or protein levels of RANKL, RANK, and proliferation markers cyclin D1 and Ki67 were assessed in various leiomyoma tissues and cell populations. Human xenograft experiments were performed to determine the effects of RANK-Fc on leiomyoma growth in vivo. Setting Research laboratory. Patients Twenty-four regularly cycling premenopausal women (age 28 to 49 years) who were not receiving hormone therapy. Interventions None. Main Outcome Measure Tumor growth in a murine xenograft model following targeting of the RANKL/RANK pathway with RANK-Fc. Results RANKL mRNA levels in leiomyoma were significantly higher than those in myometrial tissues. The highest RANK levels were found in the leiomyoma stem cell population, which is deficient in progesterone receptor (PR). Conversely, the highest RANKL levels were found in the PR-rich leiomyoma intermediate cell (LIC) population. R5020, a PR agonist, specifically increased RANKL expression in LICs. RANK-Fc blocked RANKL-induced expression of the proliferative gene cyclin D1. Treatment with RANK-Fc also significantly decreased tumor growth in vivo and diminished the expression of proliferation marker Ki67 in tumors (P &lt; 0.01; n = 4). Conclusions Treatment with the RANKL/RANK pathway inhibitor RANK-Fc significantly decreased human leiomyoma cell proliferation and tumor growth. This suggests that the RANKL/RANK pathway could serve as a potential target for the prevention and treatment of uterine leiomyoma.

scholarly journals Dysregulated heparan sulfate proteoglycan metabolism promotes Ewing sarcoma tumor growth

2021 ◽  
Author(s):  
Elena Vasileva ◽  
Mikako Warren ◽  
Timothy J Triche ◽  
James F Amatruda
Keyword(s):  
Extracellular Matrix ◽  
Tumor Growth ◽  
Heparan Sulfate ◽  
Ewing Sarcoma ◽  
Target Genes ◽  
Genetic Model ◽  
Rapid Onset ◽  
Relapsed Disease

The Ewing sarcoma family of tumors is a group of malignant small round blue cell tumors (SRBCTs) that affects children, adolescents and young adults. The tumors are characterized by reciprocal chromosomal translocations that generate chimeric fusion oncogenes, the most common of which is EWSR1-FLI1. Survival is extremely poor for patients with metastatic or relapsed disease, and no molecularly-targeted therapy for this disease currently exists. The absence of a reliable genetic animal model of Ewing sarcoma has impaired investigation of tumor cell/microenvironmental interactions in vivo. We have developed a new genetic model of Ewing sarcoma based on Cre-inducible expression of human EWSR1-FLI1 in wild type zebrafish, which causes rapid onset of SRBCTs at high penetrance. The tumors express canonical EWSR1-FLI1 target genes and stain for known Ewing sarcoma markers including CD99. Growth of tumors is associated with activation of the MAPK/ERK pathway, which we link to dysregulated extracellular matrix metabolism in general and heparan sulfate catabolism in particular. Targeting heparan sulfate proteoglycans with the specific heparan sulfate antagonist Surfen reduces ERK1/2 signaling and decreases tumorigenicity of Ewing sarcoma cells in vitro and in vivo. These results highlight the important role of the extracellular matrix in Ewing sarcoma tumor growth and the potential of agents targeting proteoglycan metabolism as novel therapies for this disease.

scholarly journals In Vivo Efficacy and Toxicity of Curcumin Nanoparticles in Breast Cancer Treatment: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Alicia S. Ombredane ◽  
Vitória R. P. Silva ◽  
Laise R. Andrade ◽  
Willie O. Pinheiro ◽  
Mayara Simonelly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Tumor Growth ◽  
Science Studies ◽  
Malignant Tumors ◽  
Stem Cell Population ◽  
Published Data ◽  
Curcumin Nanoparticles ◽  
Volume Weight

Breast cancer is one of the most prevalent types of malignant tumors in the world, resulting in a high incidence of death. The development of new molecules and technologies aiming to apply more effective and safer therapy strategies has been intensively explored to overcome this situation. The association of nanoparticles with known antitumor compounds (including plant-derived molecules such as curcumin) has been considered an effective approach to enhance tumor growth suppression and reduce adverse effects. Therefore, the objective of this systematic review was to summarize published data regarding evaluations about efficacy and toxicity of curcumin nanoparticles (Cur-NPs) in in vivo models of breast cancer. The search was carried out in the databases: CINAHL, Cochrane, LILACS, Embase, FSTA, MEDLINE, ProQuest, BSV regional portal, PubMed, ScienceDirect, Scopus, and Web of Science. Studies that evaluated tumor growth in in vivo models of breast cancer and showed outcomes related to Cur-NP treatment (without association with other antitumor molecules) were included. Of the 528 initially gathered studies, 26 met the inclusion criteria. These studies showed that a wide variety of NP platforms have been used to deliver curcumin (e.g., micelles, polymeric, lipid-based, metallic). Attachment of poly(ethylene glycol) chains (PEG) and active targeting moieties were also evaluated. Cur-NPs significantly reduced tumor volume/weight, inhibited cancer cell proliferation, and increased tumor apoptosis and necrosis. Decreases in cancer stem cell population and angiogenesis were also reported. All the studies that evaluated toxicity considered Cur-NP treatment to be safe regarding hematological/biochemical markers, damage to major organs, and/or weight loss. These effects were observed in different in vivo models of breast cancer (e.g., estrogen receptor-positive, triple-negative, chemically induced) showing better outcomes when compared to treatments with free curcumin or negative controls. This systematic review supports the proposal that Cur-NP is an effective and safe therapeutic approach in in vivo models of breast cancer, reinforcing the currently available evidence that it should be further analyzed in clinical trials for breast cancer treatments.

scholarly journals Actinomycin D downregulates Sox2 and improves survival in preclinical models of recurrent glioblastoma

2020 ◽  
Vol 22 (9) ◽  
pp. 1289-1301 ◽  
Author(s):  
Jessica T Taylor ◽  
Stuart Ellison ◽  
Alina Pandele ◽  
Shaun Wood ◽  
Erica Nathan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Population ◽  
High Throughput ◽  
Actinomycin D ◽  
Recurrent Glioblastoma ◽  
Stem Cell Population ◽  
Preclinical Models ◽  
Multicellular Spheroids

Abstract Background Glioblastoma (GBM) has been extensively researched over the last few decades, yet despite aggressive multimodal treatment, recurrence is inevitable and second-line treatment options are limited. Here, we demonstrate how high-throughput screening (HTS) in multicellular spheroids can generate physiologically relevant patient chemosensitivity data using patient-derived cells in a rapid and cost-effective manner. Our HTS system identified actinomycin D (ACTD) to be highly cytotoxic over a panel of 12 patient-derived glioma stemlike cell (GSC) lines. ACTD is an antineoplastic antibiotic used in the treatment of childhood cancers. Here, we validate ACTD as a potential repurposed therapeutic for GBM in 3-dimensional GSC cultures and patient-derived xenograft models of recurrent glioblastoma. Methods Twelve patient-derived GSC lines were screened at 10 µM, as multicellular spheroids, in a 384-well serum-free assay with 133 FDA-approved compounds. GSCs were then treated in vitro with ACTD at established half-maximal inhibitory concentrations (IC50). Downregulation of sex determining region Y–box 2 (Sox2), a stem cell transcription factor, was investigated via western blot and through immunohistological assessment of murine brain tissue. Results Treatment with ACTD was shown to significantly reduce tumor growth in 2 recurrent GBM patient-derived models and significantly increased survival. ACTD is also shown to specifically downregulate the expression of Sox2 both in vitro and in vivo. Conclusion These findings indicate that, as predicted by our HTS, ACTD could deplete the cancer stem cell population within the tumor mass, ultimately leading to a delay in tumor progression. Key Points 1. High-throughput chemosensitivity data demonstrated the broad efficacy of actinomycin D, which was validated in 3 preclinical models of glioblastoma. 2. Actinomycin D downregulated Sox2 in vitro and in vivo, indicating that this agent could target the stem cell population of GBM tumors.

scholarly journals Targeting the NCOA3-SP1-TERT axis for tumor growth in hepatocellular carcinoma

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Wenbin Li ◽  
Yue Yan ◽  
Zongheng Zheng ◽  
Qiaohua Zhu ◽  
Qian Long ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Human Telomerase Reverse Transcriptase ◽  
Nuclear Receptor Coactivator ◽  
Tert Promoter ◽  
Signaling Axis ◽  
Human Telomerase ◽  
Tert Expression

AbstractHepatocellular carcinoma (HCC) has a high mortality rate and lacks an effective therapeutic target. Elevated expression of human telomerase reverse transcriptase (TERT) is an important hallmark in cancers, but the mechanism by which TERT is activated differentially in cancers is poorly understood. Here, we have identified nuclear receptor coactivator-3 (NCOA3) as a new modulator of TERT expression and tumor growth in HCC. NACO3 specifically binds to the TERT promoter at the -234 to -144 region and transcriptionally activates TERT expression. NCOA3 promotes HCC cell growth and tumor progression in vitro and in vivo through upregulating the TERT signaling. Knockdown of NACO3 suppresses HCC cell viability and colony formation, whereas TERT overexpression rescues this suppression. NCOA3 interacts with and recruits SP1 binding on the TERT promoter. Knockdown of NCOA3 also inhibits the expression of the Wnt signaling-related genes but has no effect on the Notch signaling-targeting genes. Moreover, NCOA3 is positively correlated with TERT expression in HCC tumor tissues, and high expression of both NCOA3 and TERT predicts a poor prognosis in HCC patients. Our findings indicate that targeting the NCOA3-SP1-TERT signaling axis may benefit HCC patients.

Sign in / Sign up

Export Citation Format

Share Document