scholarly journals Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rulan Ma ◽  
Kun Zhu ◽  
Dawei Yuan ◽  
Meijun Gong ◽  
Yijun Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Bioinformatics Analysis ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Human Breast ◽  
Cancer Genome Atlas ◽  
Proliferation Assays ◽  
Proliferative Ability

Abstract Background The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC. Methods FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43. Results FBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells. Conclusion Downregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC.

scholarly journals The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells

2018 ◽  
Vol 49 (2) ◽  
pp. 432-446 ◽  
Author(s):  
Weiliang Feng ◽  
Chen Wang ◽  
Chenlu Liang ◽  
Hongjian Yang ◽  
Daobao Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
The Cancer Genome Atlas ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Migration And Invasion

Background/Aims: Next-generation sequencing (NGS) has revealed abundant long noncoding RNAs (lncRNAs) that have been characterized as critical components of cancer biology in humans. The present study aims to investigate the role of the lncRNA KCNQ1OT1 in breast cancer (BRCA) as well as the underlying molecular mechanisms and functions of KCNQ1OT1 involved in the progression of BRCA. Methods: The Cancer Genome Atlas (TCGA) and StarBase v2.0 were used to obtain the required gene data. Dual luciferase reporter gene assays were conducted to verify the relevant intermolecular target relationships. QRT-PCR and Western blot were performed to measure the expression levels of different molecules. Cell proliferation was detected by using the MTT and colony formation assays, while cell migration and invasion were examined by transwell assay. Variations in cell apoptosis and cell cycle were determined through flow cytometry. A tumor xenograft model was applied to assess tumor growth in vivo. Results: KCNQ1OT1 was found to be remarkably highly expressed in BRCA tissues and cells. KCNQ1OT1 modulated CCNE2 through sponging miR-145 in BRCA. KCNQ1OT1 promoted tumor growth in vivo by regulating miR-145/CCNE2. Conclusion: The KCNQ1OT1/miR-145/CCNE2 axis plays a critical regulatory role in BRCA, potentially giving rise to BRCA tumorigenesis and progression. These findings provide valuable evidence for improving the diagnosis and treatment of BRCA in the future.

scholarly journals Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2204
Author(s):  
Meng-Die Yang ◽  
Yang Sun ◽  
Wen-Jun Zhou ◽  
Xiao-Zheng Xie ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

scholarly journals LncRNA-SNHG6 promotes the progression of hepatocellular carcinoma by targeting miR-6509-5p and HIF1A

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoxi Fan ◽  
Zhongwei Zhao ◽  
Jingjing Song ◽  
Dengke Zhang ◽  
Fazong Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Bioinformatics Analysis ◽  
Carcinoma Cell ◽  
Noncoding Rnas ◽  
Migration And Invasion ◽  
Carcinoma Cell Lines ◽  
Huh7 Cells ◽  
Hepatocellular Carcinoma Cell

Abstract Background Accumulating evidences have been reported that long noncoding RNAs play crucial roles in the progression of hepatocellular carcinoma (HCC). SnoRNA host gene 6 (SNHG6) is believed to be involved in several human cancers, but the specific molecular mechanism of SNHG6 in HCC is not well studied. Methods In this study, we experimentally down-regulated the SNHG6 in two hepatocellular carcinoma cell lines in vitro, and then measured the proliferation, migration and invasion abilities and the apoptotic levels. Also, we performed the xenograft assay to investigate the function of SNHG6 during the tumor growth in vivo. Results We found SNHG6 was highly expressed in HCC tissues. Next, using Hep3B and Huh7 cells, we confirmed knockdown of SNHG6 reduced the proliferation, migration and invasion abilities in vitro. Also, by bioinformatics analysis, further molecular and cellular experiments, we found miR-6509-5p bound to SNHG6 directly, and the expression level of HIF1A was regulated through SNHG6/miR-6509-5p axis. Finally, we found that down-regulation of SNHG6 dramatically reduced the tumor growth ability of Huh7 cells in vivo. Conclusions We concluded that SNHG6/miR-6509-5p/HIF1A axis functioned in the progression of hepatocellular carcinoma, and could be the promising therapeutic targets during the development of hepatocellular carcinoma drugs.

scholarly journals TRIM33 Overexpression Inhibits the Progression of Clear Cell Renal Cell Carcinoma In Vivo and In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yingkun Xu ◽  
Guangzhen Wu ◽  
Jiayao Zhang ◽  
Jianyi Li ◽  
Ningke Ruan ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mrna Expression ◽  
Wnt Signaling Pathway ◽  
Xenograft Model ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels

Purpose. To evaluate the expression of tripartite motif-containing 33 (TRIM33) in ccRCC tissues and explore the biological effect of TRIM33 on the progress of ccRCC. Method. The Cancer Genome Atlas (TCGA) database was used to examine the mRNA expression levels of TRIM33 in ccRCC tissues and its clinical relevance. Immunohistochemistry (IHC) was performed to evaluate its expression in ccRCC tissues obtained from our hospital. The correlation between TRIM33 expression and clinicopathological features of the patients was also investigated. The effects of TRIM33 on the proliferation of ccRCC cells were examined using the CCK-8 and colony formation assays. The effects of TRIM33 on the migration and invasion of ccRCC cells were explored through wound healing and transwell assays, along with the use of Wnt signaling pathway agonists in rescue experiments. Western blotting was used to explore the potential mechanism of TRIM33 in renal cancer cells. A xenograft model was used to explore the effect of TRIM33 on tumor growth. Result. Bioinformatics analysis showed that TRIM33 mRNA expression in ccRCC tissues was downregulated, and low TRIM33 expression was related to poor prognosis in ccRCC patients. In agreement with this, low TRIM33 expression was detected in human ccRCC tissues. TRIM33 expression levels were correlated with clinical characteristics, including tumor size and Furman’s grade. Furthermore, TRIM33 overexpression inhibited proliferation, migration, and invasion of 786-O and ACHN cell lines. The rescue experiment showed that the originally inhibited migration and invasion capabilities were restored. TRIM33 overexpression reduced the expression levels of β-catenin, cyclin D1, and c-myc, and inhibited tumor growth in ccRCC cells in vivo. Conclusion. TRIM33 exhibits an abnormally low expression in human ccRCC tissues. TRIM33 may serve as a potential therapeutic target and prognostic marker for ccRCC.

scholarly journals SOX4 promotes the growth and metastasis of breast cancer

2020 ◽  
Author(s):  
Jing Zhang ◽  
Chunhua Xiao ◽  
Zhenbo Feng ◽  
Yun Gong ◽  
Baohua Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Lymph Nodes ◽  
Cell Viability ◽  
Cancer Cell ◽  
Chemotherapeutic Agents ◽  
Migration And Invasion ◽  
Primary Tumors

Abstract Purpose Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo . Methods We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging. Results SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo . It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel. Conclusions SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

scholarly journals Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Sarah M Peterson ◽  
Andrea Iskenderian ◽  
Lynette Cook ◽  
Alla Romashko ◽  
Kristen Tobin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Breast Cancer Xenografts

Polymalic Acid–Based Nanobiopolymer Provides Efficient Systemic Breast Cancer Treatment by Inhibiting both HER2/neu Receptor Synthesis and Activity

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Growth Inhibition ◽  
Human Breast ◽  
Akt Phosphorylation

Biodegradable nanopolymers are believed to offer great potential in cancer therapy. Here, we report thecharacterization of a novel, targeted, nanobiopolymeric conjugate based on biodegradable, nontoxic, andnonimmunogenic PMLA [poly(b-L-malic acid)]. The PMLA nanoplatform was synthesized for repetitive systemictreatments of HER2/neu-positive human breast tumors in a xenogeneic mouse model. Various moieties werecovalently attached to PMLA, including a combination of morpholino antisense oligonucleotides (AON) directedagainst HER2/neu mRNA, to block new HER2/neu receptor synthesis; anti-HER2/neu antibody trastuzumab(Herceptin), to target breast cancer cells and inhibit receptor activity simultaneously; and transferrin receptorantibody, to target the tumor vasculature and mediate delivery of the nanobiopolymer through the hostendothelial system. The results of the study showed that the lead drug tested significantly inhibited the growth ofHER2/neu-positive breast cancer cells in vitro and in vivo by enhanced apoptosis and inhibition of HER2/neureceptor signaling with suppression of Akt phosphorylation. In vivo imaging analysis and confocal microscopydemonstrated selective accumulation of the nanodrug in tumor cells via an active delivery mechanism. Systemictreatment of human breast tumor-bearing nude mice resulted in more than 90% inhibition of tumor growth andtumor regression, as compared with partial (50%) tumor growth inhibition in mice treated with trastuzumab orAON, either free or attached to PMLA. Our findings offer a preclinical proof of concept for use of the PMLAnanoplatform for combination cancer therapy.

scholarly journals Significant Inhibition of Tumor Growth following Single Dose Nanoparticle-Enhanced Photodynamic Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Shih-Hsun Cheng ◽  
Chia-Hui Chu ◽  
Nai-Tzu Chen ◽  
Jeffrey S. Souris ◽  
Chin-Tu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Human Breast Cancer ◽  
Significant Inhibition ◽  
Oxygen Species ◽  
Human Breast ◽  
Apoptotic Response ◽  
Inhibition Of Tumor Growth

Photodynamic therapy (PDT) for cancer treatment involves the pathology’s uptake of photosensitizers, which produce cytotoxic reactive oxygen species by photoirradiation. The use of nanoparticles as carriers of photosensitizers is one promising approach to this endeavor, owing to their small size, unique physicochemical properties, and easy/diverse functionalization. In the current work, we report on thein vivoassessment of PDT efficacy of these nanoconstructs in a murine model of human breast cancer, following a single (one-shot) nanoparticle dose and photoirradiation. Palladium-porphyrin (PdTPP) was administered intratumorally via injection of aqueous suspensions of either free PdTPP or MSN-conjugated PdTPP (MSN-PdTPP) at a dose of 50 μg. Mice were then exposed to a single photoirradiation session with total energy of 80 J. One month after one-shot PDT treatment, significantly greater reductions in tumor growth were observed in MSN-Pd treated animals than in PdTPP cohorts. Electron microscopy of tumor specimens harvested at various timepoints revealed excellent MSN-PdTPP uptake by cancer cells while immunohistologic analysis demonstrated marked increases in apoptotic response of MSN-PdTPP treated animals relative to PdTPP controls. Taken together, these findings suggest that considerable improvements in PDT efficacy can readily be achieved via the use of nanoparticle-based photosensitizers.

scholarly journals Saussurea lappaClarke-Derived Costunolide Prevents TNFα-Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF-κB Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Youn Kyung Choi ◽  
Sung-Gook Cho ◽  
Sang-Mi Woo ◽  
Yee Jin Yun ◽  
Jeakyung Jo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Breast Cancer Cell Growth

Saussurea lappaClarke (SLC) has been used as a traditional medicine in Korea, China, and Japan for the treatment of abdominal pain and tenesmus. Costunolide, a sesquiterpene lactone isolated from SLC, has diverse medicinal effects. However, the anticancer effects of costunolide are still unclear in breast cancer. In this study, we demonstrate that costunolide suppresses tumor growth and metastases of MDA-MB-231 highly metastatic human breast cancer cells via inhibiting TNFα-induced NF-κB activation. Costunolide inhibited MDA-MB-231 tumor growth and metastases without affecting body weights in thein vivomouse orthotopic tumor growth assays. In addition, costunolide inhibitedin vitroTNFα-induced invasion and migration of MDA-MB-231 cells. Costunolide further suppressed TNFα-induced NF-κB signaling activation, resulting in a reduced expression of MMP-9, a well-known NF-κB-dependent gene to mediate breast cancer cell growth and metastases. Therefore, we conclude that SLC and its derivative costunolide suppress breast cancer growth and metastases by inhibiting TNFα-induced NF-κB activation, suggesting that costunolide as well as SLC may be promising anticancer drugs, especially for metastatic breast cancer.

scholarly journals The human intermediate prolactin receptor is a mammary proto-oncogene

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jacqueline M. Grible ◽  
Patricija Zot ◽  
Amy L. Olex ◽  
Shannon E. Hedrick ◽  
J. Chuck Harrell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prolactin Receptor ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Mcf7 Cells ◽  
Cancer Pathogenesis ◽  
Cancer Genome Atlas ◽  
Alternatively Spliced

AbstractThe hormone prolactin (PRL) and its receptor (hPRLr) are significantly involved in breast cancer pathogenesis. The intermediate hPRLr (hPRLrI) is an alternatively-spliced isoform, capable of stimulating cellular viability and proliferation. An analogous truncated mouse PRLr (mPRLr) was recently found to be oncogenic when co-expressed with wild-type mPRLr. The goal of this study was to determine if a similar transforming event occurs with the hPRLr in human breast epithelial cells and to better understand the mechanism behind such transformation. hPRLrL+I co-expression in MCF10AT cells resulted in robust in vivo and in vitro transformation, while hPRLrI knock-down in MCF7 cells significantly decreased in vitro malignant potential. hPRLrL+I heterodimers displayed greater stability than hPRLrL homodimers, and while being capable of activating Jak2, Ras, and MAPK, they were unable to induce Stat5a tyrosine phosphorylation. Both immunohistochemical breast cancer tissue microarray data and RNA sequencing analyses using The Cancer Genome Atlas (TCGA) identified that higher hPRLrI expression associates with triple-negative breast cancer. These studies indicate the hPRLrI, when expressed alongside hPRLrL, participates in mammary transformation, and represents a novel oncogenic mechanism.

Sign in / Sign up

Export Citation Format

Share Document