scholarly journals Marine-Derived Penicillium purpurogenum Reduces Tumor Size and Ameliorates Inflammation in an Erlich Mice Model

Marine Drugs ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. 541
Author(s):  
Amanda Mara Teles ◽  
Leticia Prince Pereira Pontes ◽  
Sulayne Janayna Araújo Guimarães ◽  
Ana Luiza Butarelli ◽  
Gabriel Xavier Silva ◽  
...  
Keyword(s):  
Tumor Size ◽  
Antitumor Agents ◽  
Tumor Model ◽  
Negative Control ◽  
Lymphoid Organs ◽  
Northeastern Brazil ◽  
Mice Model ◽  
Penicillium Purpurogenum ◽  
Biotechnological Approach

Background: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. Methods: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL−), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. Results: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. Conclusions: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents.

scholarly journals Penicillium purpurogenum exerts antitumor effects and ameliorates inflammations in Erlich mice model

2020 ◽  
Author(s):  
Amanda Mara Teles ◽  
Leticia Prince Pereira Pontes ◽  
Sulayne Janayna Araujo Guimarães ◽  
Ana Luiza de Araújo Butarelli ◽  
Gabriel Xavier Silva ◽  
...  
Keyword(s):  
Tumor Model ◽  
Negative Control ◽  
Lymphoid Organs ◽  
Northeastern Brazil ◽  
Bioactive Metabolites ◽  
Mice Model ◽  
Antitumor Effects ◽  
Penicillium Purpurogenum ◽  
Biotechnological Approach

ABSTRACTBackgroundThe bioactive metabolites production contributes to the resistance of fungi towards adverse environmental conditions. Some metabolites often have interesting health-promoting activities. This study addressed the anti-tumoural properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil.MethodsThe extract obtained from the polished environment strain P. purpurogenum was fermented, filtered, concentrated and lyophilized, giving rise to the Ethyl Acetate Extracellular Extract (EAE). The metabolites of the extracellular extract of P. purpurogenum were studied using direct infusion mass spectrometry. The solid Ehrlic tumor model was used to evaluate the extract antitumor activity. Female Swiss mice were divided in groups (n=10/group) as follow: Negative control (CTL-) treated with phosphate buffered solution; Positive Control (CTL+) treated with cyclophosphamide (25mg/mL); Extracts treatment at doses 4, 20 and 100mg/Kg; Animals without tumor or treatment (Sham); and animals without tumor treated with intermediate dose (EAE20). All treatments were performed intraperitoneally, daily during 15 days. After, the animals were eutanized and the tumor, lymphoid organs and serum were used for immunological, histological and biochemical parameters evaluation.ResultsThe extract was rich in meroterpenoids. All doses of the extract significantly reduced tumor size compared to CLT- and were associated with 100% survival. Histologically, the 20 and 100mg/kg doses reduced tumour-associated inflammation and tumour necrosis. The extract also reduced cellular infiltration of lymphoid organs and circulating TNF-α levels when compared with CLT-. The extract did not induce weight loss and renal or hepatic toxic changes.ConclusionsThese results indicate that P. purpurogenum from a polluted marine environment produce hybrid natural products of the terpenoid pathway that exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a biotechnological approach for the production of antitumour agents.

scholarly journals Antiproliferation Effects of Nanophytosome-Loaded Phenolic Compounds From Fruit of Juniperus Polycarpos Against Breast Cancer in Mice Model: Synthesis, Characterization and Therapeutic Effects

2021 ◽  
Author(s):  
Soheila Moeini ◽  
Ehsan Karimi ◽  
Ehsan Oskoueian
Keyword(s):  
Breast Cancer ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Fruit Extract ◽  
Phenolic Fraction ◽  
Juniperus Polycarpos

Abstract Background: This research was performed to synthesize nanophytosomes-loaded high phenolic fraction (HPF) from Juniperus polycarpos fruit extract and investigate its antiproliferation effects against breast cancer in mice model. Results: The nanophytosomes-loaded HPF from Juniperus polycarpos fruit extract was synthesized. The mice trial was conducted to determine the possible toxic effects of the synthesized nanophytosomes. The anticancer, pro-apoptotic, and antioxidative activities of the nanophytosomes were determined. The nanophytosomes-loaded HPF had a spherical structure with a size of 176 nm and a polydispersity index coefficient of 0.24. The in-vivo study manifested that nanophytosomes-loaded HPF significantly improved weight gain and food intake compared to the negative control group (p<0.05). The nanophytosomes-loaded HPF significantly enhanced the expression of bax (3.4-fold) and caspase-3 (2.7-fold) genes but reduced bcl2 (3.6-fold) gene expression in tumor cells. The average tumor size was significantly decreased in mice treated with nanophytosomes-loaded HPF (p<0.05). The expression of GPX (2.3-fold) and SOD (2.7-fold) antioxidants in the liver of mice supplemented with nanophytosomes-loaded HPF was significantly developed compared to the negative control (p<0.05). The nanophytosomes-loaded HPF did not show toxicity on normal cells. Conclusion: Our results indicated that nanophytosomes-loaded HPF might be a potential anticancer agent for the breast cancer treatment.

ANKHD1 Silencing Reduces In Vitro Clonogenicity and In Vivo Tumorogenicity Of Multiple Myeloma Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3168-3168
Author(s):  
Anamika Dhyani ◽  
João Agostinho Machado-Neto ◽  
Patricia Favaro ◽  
Sara Teresinha Olalla Saad
Keyword(s):  
Cell Cycle ◽  
Gene Therapy ◽  
Multiple Myeloma ◽  
Cell Lines ◽  
Tumor Size ◽  
Control Group ◽  
Mice Model ◽  
And Migration

Abstract Introduction ANKHD1 is a multiple ankyrin repeats containing protein, highly expressed in cancers, such as acute leukemia. Earlier studies showed that ANKHD1 is highly expressed and plays important role in proliferation and cell cycle progression of multiple myeloma (MM) cells. It was also observed that ANKHD1 downregulation modulates cell cycle gene expression and upregulates p21 irresepective of TP53 mutational status of MM cell lines. Objective The present study aimed to study the effect ofANKHD1 silencing on MM growth both in vitro (clonogenicity, migration) and in vivo (xenograft tumor mice model). The purpose was to investigate the feasibility of ANKHD1 gene therapy for MM. Methods In the present study, ANKHD1 expression was silenced using short hairpin RNA (shRNA)-lentiviral delivery vector in MM cell lines (U266 and MM1S). For control MM cells were tranduced by lentiviral shRNA against LacZ. Downregulation of ANKHD1 expression was confirmed by qPCR and Western blot. Colony formation capacity and migration of control and ANKHD1 silenced MM cells was determined by methylcellulose and transwell migration assays, respectively. For in vivo MM growth, NOD-SCID mice were divided in two groups injected with control and ANKHD1 silenced cells, separately. Mice were observed daily for tumor growth. Once the tumor size reached 1 mm3, mice in both groups were sacrificed and tumor was excised to measure tumor volume and weight. Results Corroborating the results obtained in our earlier studies, in the present study also inhibition of ANKHD1 expression suppressed growth of MM cells in vitro. MM cell lines tranduced with ANKHD1 shRNA showed significantly low number of colonies ten days after plating in methylcellulose medium as compared to control (p<0.05). Similarly, in transwell migration assay, cell lines transduced with ANKHD1 showed significantly less migration as in response to 10% FBS at lower chamber as compared to control group (p<0.05) in both the cell lines analyzed. Further in xenograft MM mice model, the growth of tumor was visibly suppressed in mice injected with ANKHD1 silenced cells compared to control group. There was significant difference in tumor size (volume) between these 2 groups (P< 0.006). The tumor weight of the inhibition group was 0.71 ±0.2 g, significantly lighter than those of the control group (1.211 ± 0.5 g, P =0.02) Conclusion Our data indicates ANKHD1 downregulation significantly inhibits colony-forming ability and migration of both glucocorticoid resistant (U266) and sensitive (MM1S) MM cells. Further, gene silencing of ANKHD1 also resulted in reduced in vivo tumor growth in NOD/SCID mice. Collectively, the result obtained indicates that ANKHD1 may be a target for gene therapy in MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The tumor suppressor miR-642a-5p targets Wilms Tumor 1 gene and cell-cycle progression in prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dianne J. Beveridge ◽  
Kirsty L. Richardson ◽  
Michael R. Epis ◽  
Rikki A. M. Brown ◽  
Lisa M. Stuart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Wilms Tumor ◽  
Tumor Model ◽  
Negative Control ◽  
Wilms Tumor 1

AbstractRNA-based therapeutics are emerging as innovative options for cancer treatment, with microRNAs being attractive targets for therapy development. We previously implicated microRNA-642a-5p (miR-642a-5p) as a tumor suppressor in prostate cancer (PCa), and here we characterize its mode of action, using 22Rv1 PCa cells. In an in vivo xenograft tumor model, miR-642a-5p induced a significant decrease in tumor growth, compared to negative control. Using RNA-Sequencing, we identified gene targets of miR-642a-5p which were enriched for gene sets controlling cell cycle; downregulated genes included Wilms Tumor 1 gene (WT1), NUAK1, RASSF3 and SKP2; and upregulated genes included IGFBP3 and GPS2. Analysis of PCa patient datasets showed a higher expression of WT1, NUAK1, RASSF3 and SKP2; and a lower expression of GPS2 and IGFBP3 in PCa tissue compared to non-malignant prostate tissue. We confirmed the prostatic oncogene WT1, as a direct target of miR-642a-5p, and treatment of 22Rv1 and LNCaP PCa cells with WT1 siRNA or a small molecule inhibitor of WT1 reduced cell proliferation. Taken together, these data provide insight into the molecular mechanisms by which miR-642a-5p acts as a tumor suppressor in PCa, an effect partially mediated by regulating genes involved in cell cycle control; and restoration of miR-642-5p in PCa could represent a novel therapeutic approach.

scholarly journals Antimalarial Activity of Meriandra dianthera Leaf Extracts in Plasmodium berghei-Infected Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Kalay Hagazy ◽  
Gereziher G. Sibhat ◽  
Aman Karim ◽  
Gebretsadkan H. Tekulu ◽  
Gomathi Periasamy ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Leaf Extract ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Mice Model ◽  
Oral Toxicity ◽  
Leaf Extracts ◽  
Traditional Use ◽  
Crude Leaf Extract

Objective. To evaluate the antimalarial effect of aqueous methanolic extract and solvent fractions of Meriandra dianthera leaves against Plasmodium berghei in mice model. Method. M. dianthera leaves were extracted with 80% methanol and dried. The dried crude extract was then defatted and further fractionated with chloroform, ethyl acetate, and butanol. Acute oral toxicity test was performed as per the Organization for Economic Cooperation and Development guideline 425. Peter’s 4-day suppressive test was used to determine the in vivo antimalarial activity of the extract and fractions. Result. The crude leaf extract of Meriandra dianthera showed parasite inhibition of 42.28% and 45.52% at doses of 400 and 600 mg/kg, respectively, as compared to the negative control. Moreover, the mice which received chloroform and aqueous fractions at the dose of 400 mg/kg/day showed significant (P<0.001) chemosuppression compared to the negative control. Both the extract and fractions were able to prevent P. berghei induced body weight loss and body temperature reduction and also increased the survival time of the mice as compared to the negative control. The aqueous methanolic leaf extract of M. dianthera showed no gross signs of toxicity or mortality in mice until a single oral dose of 2000 mg/kg. Conclusion. The extracts of M. dianthera leaves showed promising antimalarial activity, with no sign of toxicity and therefore may support its traditional use for the treatment of malaria.

scholarly journals In vivo antimalarial activity of crude fruit extract of Capsicum frutescens var. minima (Solanaceae) against Plasmodium berghei infected mice

2020 ◽  
Author(s):  
Getu Habte ◽  
Solomon Assefa
Keyword(s):  
Survival Time ◽  
Antimalarial Activity ◽  
Antimalarial Drugs ◽  
Negative Control ◽  
Antiplasmodial Activity ◽  
Capsicum Frutescens ◽  
Mice Model ◽  
Fruit Extract ◽  
Dose Levels

Abstract Background: The alarming spread of drug resistance to current antimalarial agents is threatening malaria controlling efforts. This, consequently, urged the scientific community to discover novel antimalarial drugs. Successful and most potent antimalarial drugs were obtained from medicinal plants. Capsicum frutescens is claimed to possess an antiplasmodial activity in Ethiopian and Ugandan folkloric medicine. However, there is lack of pharmacological evidence for its antiplasmodial activity. This study, hence, was aimed at evaluating the in vivo antiplasmodial activity of C. frutescens in mice model. Methods: The 4-day suppressive test was employed to ascertain the claimed antiplasmodial effect of the plant. Following inoculation with P. berghei , mice in treatment groups were provided with three dose levels (100, 200 and 400 mg/kg) of the extract. Whereas, 2% Tween80 and chloroquine served as negative and positive control, respectively. Weight, temperature, packed cell volume, parasitemia and survival time were then monitored.Results: The oral acute toxicity study revealed that the crude extract caused no mortality and revealed no overt sign of toxicity. In 4-day suppressive test, all dose levels of the extract was found to exhibit a significant (p<0.05) inhibition of parasitemia compared to negative control. Maximum parasite suppression (93.28%) was exerted by the highest dose (400mg/kg/day) of extract. In addition, the extract significantly (p<0.05) prolonged survival time and prevented body weight loss, reduction in temperature and anemia compared to vehicle treated group.Conclusion: This investigation found a strong evidence that fruit extract of C. frutescens is endowed with a promising antiplasmodial activity. Hence, the plant could serve as a potential source of newer antimalarial agent.

scholarly journals Novel Intratumoral Treatment With 5-Androstene-3b, 17a-Diol Inhibits Tumor Size and Metastasis In a Mice Model

2021 ◽  
Author(s):  
Rocio Alejandra Ruiz-Manzano ◽  
Margarita Isabel Palacios-Arreola ◽  
Rosalia Hernandez-Cervantes ◽  
Victor Hugo Del Rio-Araiza ◽  
Karen Elizabeth Nava-Castro ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Size ◽  
Breast Tumor ◽  
Human Cancer ◽  
Tumor Model ◽  
Vehicle Group ◽  
Mice Model ◽  
Human Cancer Cell Lines

Abstract Background: Breast cancer treatment-failure is related to low compliance rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic and cheaper treatments. The epimereandrostene-3beta,17alpha-diol (α-AED) has been proven to inhibit breast tumor cell proliferation in vitro, being an ideal candidate to treat mammary tumors. The aim of this study was to evaluate the in situ effects of α-AED on tumor mammary growth. 4T1 tumors with 14 days of growth were injected with an equivalent dose to the IC50 (100 mM) and its double concentration (200 mM) of α-AED. Methods: The cell viability and cell proliferation of murine and human cancer cell lines after the treatment of α-AED were evaluated with sulforhodamine assay and bromodeoxyuridine incorporation, respectively. We also evaluated the size and tumor growth of the orthotopic tumor model after the treatment with α-AED. The tumor infiltration changes and cytokine determination into the tumor microenvironment were determined by flow cytometry and ELISA methods, respectively. The humoral response denoted by the production fo IgG anti-4T1 antibodies were also determined by ELISA methd. Results: Low and high concentrations of α-AED administrated intratumorally reduce the size and average tumor. α-AED also increased the percentages of NK, plasmatic and plasmablast cells in mice tumors injected with 100 mM of a-AED. Meanwhile, tumors injected with 200 mM of a-AED contained an elevated proportion of plasmablast and B cells. Of notice, VEGF levels in all a-AED-treated tumors were lower than the control and vehicle group. The tumor in situ response was reflected systemically by the increase of the anti-4T1 IgG in serum from a-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for to the local injection of a-AED is produced by the anti-proliferative effect of this hormone, that maybe associated to the VEGF reduction and metastasis. Conclusion: We observed an astonishing tumor size reduction and metastasis after the treatment with a-AED. The above suggest that a-AED can be used in clinical studies in order to prove its efficacy as an alternative of novel breast tumor treatment.

Development of Improved Lentiviral ‘Suicide’ Gene Therapy for the Management of GvHD and GvL/GvT Responses in Allogeneic BMT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3256-3256
Author(s):  
Anton Neschadim ◽  
Takeya Sato ◽  
Daniel H. Fowler ◽  
Arnon Lavie ◽  
Jeffrey A. Medin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Tumor Size ◽  
Tumor Model ◽  
Suicide Gene ◽  
Dependent Manner ◽  
Empty Vector ◽  
Donor T Cells

Abstract Donor Lymphocyte Infusion (DLI) is employed in the treatment of various malignancies, as donor-derived allogeneic T lymphocytes elicit strong anti-tumor immune responses (GvL/GvT). Unfortunately, these are often accompanied by GvHD, mediated by donor T cells that are allo-activated against host tissues. GvHD manifests with immunosupression, multi-organ dysfunction, severe morbidity and high mortality. It is suggested that CD4+Th1 and CD8+Tc1 cell subsets mediate both strong GvL/GvT and strong GvHD, while being cross-regulated by CD4+Th2 and CD8+Tc2 cells that mediate only moderate effects. Patients transplanted with T cell-depleted BM experience little GvHD, but have high rates of cancer relapse. It is possible to maintain beneficial GvL/GvT responses while controlling GvHD by transferring a drug-activating ‘suicide’ gene into donor T cells prior to transplant. Cells expressing the ‘suicide’ gene-product convert a non-toxic prodrug into a cytotoxic antimetabolite, and are eliminated by apoptosis. We have constructed 3rd generation lentiviral vectors (LVs) for the expression of human converting enzymes. We are using novel enzymes, endogenously present in human cells, to avoid unwanted immune responses against vector-transduced cells, recently proven a major drawback in clinical trials. Our approaches are based on the human thymidylate kinase (Tmpk), which acts on Zidovudine (AZT), and the human deoxycytidine kinase (dCK), which potently activates a number of prodrugs, including Cytarabine (AraC), Gemcitabine and Cladribine. We have developed active-site engineered mutants of Tmpk and dCK that are up to two orders of magnitude more catalytically active than wild-type (wt) enzymes. Our LVs efficiently transduce both immortalized and primary cells (up to 99%). The LV expression cassette also encodes a non-signaling form of human CD19 molecule that serves as a marker for ex vivo enrichment and in vivo tracking of transduced cells. We demonstrate efficient, selective and prompt killing of transduced cells in a dose-dependent manner by a number of prodrugs in cell lines in vitro and in a murine solid tumor model in vivo. For example, R16GLL Tmpk mutant-transduced Jurkat cells (human T cell leukemia line) are completely killed by apoptosis within 4 days of culture in media containing 100uM AZT (IC50 of 2μM), while wt cells are unaffected at the same conditions. In a NOD/SCID murine tumor model, K562 erythroid leukemia cells transduced with either empty vector, wt Tmpk, and R16GLL or F105Y Tmpk mutants were implanted subcutaneously. Mice bearing tumor cells expressing either R16GLL or F105Y Tmpk and receiving a low daily dose of 2.5mg/kg of AZT have developed significantly reduced tumors following 2 weeks of treatment (tumor size of 24–200mm2), compared to mice bearing wt Tmpk and empty vector transduced cells, or untreated mice (tumor size of over 1000mm2). We are currently evaluating the efficiency with which transduced cells can be cleared from circulation in a murine leukemia model and are evaluating the complete GvHD-treatment strategy in a murine model of GvHD/GvT based on the CD45 congenic strains. This much improved therapeutic strategy may offer a safe and complete solution for GvHD in patients undergoing BMT.

CircRNA-104718 acts as competing endogenous RNA and promotes hepatocellular carcinoma progression through microRNA-218-5p/TXNDC5 signaling pathway

2019 ◽  
Vol 133 (13) ◽  
pp. 1487-1503 ◽  
Author(s):  
Jiaze Yu ◽  
Minjie Yang ◽  
Bo Zhou ◽  
Jianjun Luo ◽  
Zihan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Tumor Size ◽  
Cancer Biology ◽  
Underlying Mechanism ◽  
Vital Role ◽  
In Vivo Studies ◽  
Circular Rnas ◽  
Mice Model

AbstractAccumulating evidences indicate that circular RNAs (circRNAs) play a vital role in diverse cancer biology. However, the contributions of circRNAs to hepatocellular carcinoma (HCC) and their underlying mechanism remain largely unknown. The present study aims at investigating the role of circRNA-104718 in HCC progression, which has been observed to be significantly up-regulated in HCC tissues. We found that, higher expression of circRNA-104718 also leds to a poor prognosis in HCC patients. Using luciferase binding assays and RNA immunoprecipitation studies, we identified circRNA-104718 is physically associated and co-expressed with microRNA (miR)-218-5p in HCC. Mechanistically, we demonstrated that circRNA-104718 functions as a competing endogenous RNAs (ceRNAs) and competes with thioredoxin domain-containing protein 5 (TXNDC5) mRNA and directly binds to miR-218-5p. Functionally, we found that ectopically expressed circRNA-104718 accelerated cell proliferation, migration, invasion, and inhibited apoptosis. In vivo studies on a nude mice model showed that circRNA-104718 overexpression could increase the tumor size and the rate of metastasis. Silencing of circRNA-104718 could decrease both the tumor size and metastasis significantly. Conversely, we also observed overexpression of miR-218-5p could in turn decrease the proliferation, migration, invasion, and increase apoptosis. Furthermore, circRNA-104718 could relieve the suppression of miR-218-5p target TXNDC5 and thereby cause an inhibition of miR’s functions. In summary, our results indicate that circRNA-104718 acts as a ceRNA and promotes HCC progression through the targeting of miR-218-5p/TXNDC5 signaling pathway. Thus, we propose that circRNA-104718 would be a promising target for HCC diagnosis and therapy.

scholarly journals A novel tumor suppressor ASMTL-AS1 regulates the miR-1228-3p/SOX17/β-catenin axis in triple‐negative breast cancer

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jie Sun ◽  
Xiaohua Li ◽  
Enqiao Yu ◽  
Jianxia Liu ◽  
Liang Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Mice Model ◽  
Normal Tissues ◽  
Tnbc Cell

Abstract Background Triple-negative breast cancer (TNBC) is a special type of breast cancer that lacks effective therapeutic targets. There is a significant need to clarify its pathogenesis, so as to bring new targeted approaches for TNBC management. Here, we identified a long-non coding RNA (lncRNA) ASMTL-AS1 that linked to TNBC development and progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were used to test gene and protein levels, respectively. The regulatory axis of miR-1228-3p/SOX17/β-catenin was determined by luciferase reporter and RNA pull-down assays. In vivo assay was conducted by using the nude mice model via subcutaneous transplantation of tumor cells. Results ASMTL-AS1 was significantly downregulated in TNBC tissues compared to normal tissues, which was closely associated with aggressive clinical features and unfavorable prognosis. Lentivirus-mediated ASMTL-AS1 overexpression evidently reduced the ability of TNBC cell colony formation, activity and invasion by more than 2.5 times. RNA pull-down and luciferase reporter assays revealed that miR-1228-3p directly bound to ASMTL-AS1, ASMTL-AS1 increased SOX17 expression via sponging and repressing miR-1228-3p. Subsequently, the upregulated SOX17 trans-suppressed β-catenin expression, resulting in the inactivation of carcinogenic Wnt/β-catenin signaling, thereby restraining TNBC cell growth and dissemination. Importantly, the xenograft tumor model showed that the ASMTL-AS1 overexpression significantly retarded tumor growth, and negatively regulated Wnt/β-catenin pathway. Conclusions Our data characterize a novel tumor suppressor in TNBC, restoration of ASMTL-AS1 may be a candidate therapeutic intervention for TNBC patients.

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