scholarly journals Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 118
Author(s):  
Heejoo Kim ◽  
Hwee Won Ji ◽  
Hyeon Woo Kim ◽  
Sung Hwan Yun ◽  
Jae Eun Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
In Silico ◽  
Noncoding Rna ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Gene Prediction ◽  
Noncoding Rnas ◽  
Ginsenoside Rg3 ◽  
Mcf 7

Ginsenoside Rg3 exerts antiproliferation activity on cancer cells by regulating diverse noncoding RNAs. However, little is known about the role of long noncoding RNAs (lncRNAs) or their relationship with competitive endogenous RNA (ceRNA) in Rg3-treated cancer cells. Here, a lncRNA (ATXN8OS) was found to be downregulated via Rg3-mediated promoter hypermethylation in MCF-7 breast cancer cells. SiRNA-induced downregulation of ATXN8OS decreased cell proliferation but increased apoptosis, suggesting that the noncoding RNA possessed proproliferation activity. An in silico search for potential ATXN8OS-targeting microRNAs (miRs) identified a promising candidate (miR-424-5p) based on its high binding score. As expected, miR-424-5p suppressed proliferation and stimulated apoptosis of the MCF-7 cells. The in silico miR-target-gene prediction identified 200 potential target genes of miR-424-5p, which were subsequently narrowed down to seven that underwent hypermethylation at their promoter by Rg3. Among them, three genes (EYA1, DACH1, and CHRM3) were previously known oncogenes and were proven to be oppositely regulated by ATXN8OS and miR-424-5p. When taken together, Rg3 downregulated ATXN8OS that inhibited the tumor-suppressive miR-424-5p, leading to the downregulation of the oncogenic target genes.

scholarly journals d Rhamnose β-hederin reverses chemoresistance of breast cancer cells by regulating exosome-mediated resistance transmission

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Wei-xian Chen ◽  
Ling-yun Xu ◽  
Qi Qian ◽  
Xiao He ◽  
Wen-ting Peng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Gene ◽  
Gene Prediction ◽  
Docetaxel Resistance ◽  
Resistance Reversal ◽  
Mcf 7 ◽  
Chinese Medicinal Plant

d Rhamnose β-hederin (DRβ-H), an active component extracted from the traditional Chinese medicinal plant Clematis ganpiniana, has been reported to be effective against breast cancer. Recent studies have also indicated that the isolated exosomes (D/exo) from docetaxel-resistant breast cancer cells MCF-7 (MCF-7/Doc) were associated with resistance transmission by delivering genetic cargo. However, the relevance of D/exo during DRβ-H exposure remains largely unclear. In the present work, exosomes were characterized by morphology and size distribution. We reinforced the significant role of D/exo in spreading chemoresistance from MCF-7/Doc to recipient sensitive cells after absorption and internalization. DRβ-H could reduce the formation and release of D/exo. Next, we demonstrated that DRβ-H was able to reverse docetaxel resistance and that D/exo was responsible for DRβ-H-mediated resistance reversal. We also found that DRβ-H could decrease the expressions of several most abundant miRNAs (miR-16, miR-23a, miR-24, miR-26a, and miR-27a) transported by D/exo. Target gene prediction and pathway analysis showed the involvement of these selected miRNAs in pathways related to treatment failure. Our results suggested that DRβ-H could reduce D/exo secretion from MCF-7/Doc cells and induce the reduction in resistance transmission via D/exo.

scholarly journals Global transcriptome analysis reveals partial estrogen-like effects of karanjin in MCF-7 breast cancer cells

2021 ◽  
Author(s):  
Gaurav Bhatt ◽  
Akshita Gupta ◽  
Latha Rangan ◽  
Anil Mukund Limaye
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Biological Activities ◽  
Biological Effects ◽  
Dependent Manner ◽  
Cell Type ◽  
Concentration Dependent Manner ◽  
Mcf 7

Karanjin, an abundantly occurring furanoflavonoid in edible and non-edible legumes, exerts diverse biological effects in vivo, and in vitro. Its potential as an anticancer agent is also gaining traction following recent demonstrations of its anti-proliferative, cell cycle inhibitory, and pro-apoptotic effects. However, the universality of its anticancer potential is yet to be scrutinized, particularly so because flavonoids can act as selective estrogen receptor modulators (SERMs). Even the genomic correlates of its biological activities are yet to be examined in hormone responsive cells. This paper presents the early and direct transcriptomic footprint of 10 μM karanjin in MCF-7 breast cancer cells, using next generation sequencing technology (RNA-seq). We show that karanjin-modulated gene-expression repertoire is enriched in several hallmark gene sets, which include early estrogen-response, and G2/M checkpoint genes. Genes modulated by karanjin overlapped with those modulated by 1 nM 17β-estradiol (E2), or 1 μM tamoxifen. Karanjin altered the expression of selected estrogen-regulated genes in a cell-type, and concentration dependent manner. It downmodulated the expression of ERα protein in MCF-7 cells. Furthermore, ERα knockdown negatively impacted karanjins ability to modulate the expression of selected E2 target genes. Our data suggest that karanjin exerts its effects on ERα-positive breast cancer cells, at least in part, via ERα. The apparent SERM-like effects of karanjin pose a caveat to the anticancer potential of karanjin. In-depth studies on cell-type and concentration-dependent effects of karanjin may bring out its true potential in endocrine therapies.

Synthesis and In Vitro Evaluation of Tetrahydroquinoline Derivatives as Antiproliferative Compounds of Breast Cancer via Targeting the GPER

2019 ◽  
Vol 19 (6) ◽  
pp. 760-771 ◽  
Author(s):  
Oscar J. Zacarías-Lara ◽  
David Méndez-Luna ◽  
Gustavo Martínez-Ruíz ◽  
José R. García-Sanchéz ◽  
Manuel J. Fragoso-Vázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
In Silico ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
In Silico Studies ◽  
Mcf 7

Background: Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells. Objective: In an effort to develop new therapeutic strategies against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA. Methods: This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines. Results: In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and molecular dynamics simulations of the target compounds were performed with GPER to explore their binding mode and free energy values. In addition, the target small molecules were synthesized and assayed in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands reach the GPER-binding site in a similar way, as was demonstrated through in silico studies. Conclusion: A concentration-dependent inhibition of cell proliferation occurred with compound 2 in the two cell lines regardless of GPER.

scholarly journals Transcription factor EGR3 is involved in the estrogen-signaling pathway in breast cancer cells

2004 ◽  
Vol 32 (3) ◽  
pp. 649-661 ◽  
Author(s):  
A Inoue ◽  
Y Omoto ◽  
Y Yamaguchi ◽  
R Kiyama ◽  
SI Hayashi
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Alpha ◽  
Target Genes ◽  
Estrogen Signaling ◽  
Upstream Region ◽  
Custom Made ◽  
Mcf 7

Estrogen has been closely associated with the genesis and malignant progression of breast cancer. However, the molecular mechanism underlying the effects of estrogen is far from being completely clarified. We previously developed a custom-made cDNA microarray consisting of approximately 200 estrogen-responsive genes in breast cancer cells. Using this system, we found one estrogen-induced gene in various cancer cell lines, including breast cancer MCF-7 cells, which encode a zinc-finger transcription factor, EGR3 (early growth response 3). Northern blot analysis of estradiol-treated MCF-7 cells showed rapid and robust induction of Egr3, and addition of cycloheximide or ICI 182,780 suggested that Egr3 is the bona fide target for the estrogen receptor alpha (ERalpha). Using stable transformants derived from MCF-7 cells which were transfected with expression-controllable Egr3-expression vector, we demonstrated that Nab2 is one of the target genes for EGR3. Microarray analysis of the transformants revealed other candidate EGR3-induced genes. These strategies could be useful for analyzing downstream genes of ERalpha, and may contribute to elucidating the extensive signaling network of estrogen stimuli. Furthermore, a reporter assay using the upstream region of fasL probably involving escape from the immune system revealed that fasL is another target gene for EGR3. The roles of EGR3 in the physiology of breast cancer are discussed.

scholarly journals β-Elemene Reverses Chemoresistance of Breast Cancer Cells by Reducing Resistance Transmission via Exosomes

2015 ◽  
Vol 36 (6) ◽  
pp. 2274-2286 ◽  
Author(s):  
Jun Zhang ◽  
He-da Zhang ◽  
Yu-Feng Yao ◽  
Shan-Liang Zhong ◽  
Jian Hua Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Mirna Expression ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Real Time Quantitative Pcr ◽  
The Impact ◽  
Mcf 7 ◽  
In Cells

Background: Currently, exosomes that act as mediators of intercellular communication are being researched extensively. Our previous studies confirmed that these exosomes contain microRNAs (miRNAs) that could alter chemo-susceptibility, which is partly attributed to the successful intercellular transfer of multidrug resistance (MDR)-specific miRNAs. We also confirmed that β-elemene could influence MDR-related miRNA expression and regulate the expression of the target genes PTEN and Pgp, which may lead to the reversal of the chemoresistant breast cancer (BCA) cells. We are the first to report these findings, and we propose the following logical hypothesis: β-elemene can mediate MDR-related miRNA expression in cells, thereby affecting the exosome contents, reducing chemoresistance transmission via exosomes, and reversing the drug resistance of breast cancer cells. Methods: MTT-cytotoxic, miRNA microarray, real-time quantitative PCR, Dual Luciferase Activity Assay, and Western blot analysis were performed to investigate the impact of β-elemene on the expression of chemoresistance specific miRNA and PTEN as well as Pgp in chemoresistant BCA exosomes. Results: Drug resistance can be reversed by β-elemene related to exosomes. There were 104 differentially expressed miRNAs in the exosomes of two chemoresistant BCA cells: adriacin (Adr) - resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) that underwent treatment. Of these, 31 miRNAs were correlated with the constant changes in the MDR. The expression of miR-34a and miR-452 can lead to changes in the characteristics of two chemoresistant BCA exosomes: MCF-7/Adr exosomes (A/exo) and MCF-7/Doc exosomes (D/exo). The PTEN expression affected by β-elemene was significantly increased, and the Pgp expression affected by β-elemene was significantly decreased in both cells and exosomes. β-elemene induced a significant increase in the apoptosis rate in both MCF-7/Doc and MCF-7/Adr cells. Conclusions: Drug resistance can be reversed by β-elemene, which can alter the expression of some MDR-related miRNAs, including PTEN and Pgp in MCF-7/Adr and MCF-7/Doc in cells. It can therefore affect the exosome contents and induce the reduction of resistance transmission via exosomes.

scholarly journals Stable Inhibition of Specific Estrogen Receptor α (ERα) Phosphorylation Confers Increased Growth, Migration/Invasion, and Disruption of Estradiol Signaling in MCF-7 Breast Cancer Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4144-4159 ◽  
Author(s):  
B. P. Huderson ◽  
T. T. Duplessis ◽  
C. C. Williams ◽  
H. C. Seger ◽  
C. G. Marsden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Expression Patterns ◽  
Estrogen Receptor Α ◽  
Regulated Gene Expression ◽  
Mcf 7

Elevated phosphorylation of estrogen receptor α (ERα) at serines 118 (S118) and 167 (S167) is associated with favorable outcome for tamoxifen adjuvant therapy and may serve as surrogate markers for a functional ERα signaling pathway in breast cancer. It is possible that loss of phosphorylation at S118 and/or S167 could disrupt ERα signaling, resulting in aggressive ERα-independent breast cancer cells. To this end, MCF-7 breast cancer cells were stably transfected with an ERα-specific short hairpin RNA that reduced endogenous ERα. The resulting cell line was stably transfected with wild-type ERα (ER-AB cells), or ERα containing serine to alanine mutation at S118 or S167 (S118A cells and S167A cells, respectively). These stable cell lines expressed approximately equivalent ERα compared with parental MCF-7 cells and were evaluated for growth, morphology, migration/invasion, and ERα-regulated gene expression. S118A cells and S167A cells exhibited increased growth and migration/invasion in vitro. Forward- and side-scatter flow cytometry revealed that S167A cells were smaller in size, and both S118A and S167A cells exhibited less cellular complexity. S118A and S167A cells expressed pancytokeratin and membrane localization of β-catenin and did not express vimentin, indicating retention of epithelial lineage markers. Expression of ERα-target genes and other genes regulated by ERα signaling or involved in breast cancer were markedly altered in both S118A and S167A cells. In summary, attenuated phosphorylation of ERα at S118 and S167 significantly affected cellular physiology and behavior in MCF-7 breast cancer cells, resulting in increased growth, migration/invasion, compromised expression of ERα target genes, and markedly altered gene expression patterns.

scholarly journals ZNRD1 and Its Antisense Long Noncoding RNA ZNRD1-AS1 Are Oppositely Regulated by Cold Atmospheric Plasma in Breast Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Hyeon Woo Kim ◽  
Dawoon Jeong ◽  
Juyeon Ham ◽  
Heejoo Kim ◽  
Hwee Won Ji ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Cells ◽  
Atmospheric Plasma ◽  
Cancer Tissue ◽  
Dependent Manner ◽  
Cold Atmospheric Plasma ◽  
Mcf 7

Cold atmospheric plasma (CAP) has been recognized as a potential alternative or supplementary cancer treatment tool, which is attributed by its selective antiproliferation effect on cancer cells over normal cells. Standardization of the CAP treatment in terms of biological outputs such as cell growth inhibition and gene expression change is essential for its clinical application. This study aims at identifying genes that show consistent expression profiles at a specific CAP condition, which could be used to monitor whether CAP is an appropriate treatment to biological targets. To do this, genes showing differential expression by two different CAP treatment conditions were screened in the MCF-7 breast cancer cells. As a result, ZNRD1 was identified as a potential marker with being consistently upregulated by 600 s but downregulated by the 10×30 s CAP treatment scheme. Expression of ZNRD1 was increased in breast cancer tissues compared to normal tissues, judged by cancer tissue database analysis, and supported by the antiproliferation after siRNA-induced downregulation in MCF-7. Interestingly, the antisense long noncoding RNA (lncRNA) of ZNRD1, ZNRD1-AS1, was regulated to the opposite direction of ZNRD1 by CAP. The siRNA-based qPCR analysis indicates that ZNRD1 downregulates ZNRD1-AS1, but not vice versa. ZNRD1-AS1 was shown to increase a few cis-genes such as HLA-A, HCG9, and PPP1R11 that were also regulated by CAP. Altogether, this study identified a pair of gene and its antisense lncRNA of which expression is precisely controlled by CAP in a dose-dependent manner. These genes could help elucidate the molecular mechanism how CAP regulates lncRNAs in cancer cells.

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