LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway

2019 ◽  
Vol 41 (9) ◽  
pp. 1273-1281 ◽  
Author(s):  
Kai Fang ◽  
Caixia Hu ◽  
Xiufen Zhang ◽  
Yafei Hou ◽  
Danfeng Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
P38 Mapk ◽  
The Cancer Genome Atlas ◽  
Mitogen Activated Protein Kinase ◽  
High Expression ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Mapk Signalling ◽  
And Migration

Abstract Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared with the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with estrogen receptor-negative, progesterone receptor-negative, advanced tumour-node-metastasis stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 mitogen-activated protein kinase (MAPK) gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

scholarly journals Echinacoside Suppresses the Progression of Breast Cancer by Downregulating the Expression of miR-4306 and miR-4508

2021 ◽  
Vol 20 ◽  
pp. 153473542110626
Author(s):  
Peng Bian ◽  
Chuan Liu ◽  
Wei Hu ◽  
Yu Ding ◽  
Shusheng Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effect ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Anticancer Effects ◽  
And Migration ◽  
Cancer Tissues

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

scholarly journals A Novel Role for Brain and Acute Leukemia Cytoplasmic (BAALC) in Human Breast Cancer Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Madeleine Birgersson ◽  
Mengna Chi ◽  
Chrissy Miller ◽  
Joshua S. Brzozowski ◽  
Jeffrey Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Normal Breast ◽  
Migration And Invasion ◽  
Free Survival ◽  
Invasion And Migration ◽  
And Migration ◽  
Disease Free

Brain and Acute Leukemia, Cytoplasmic (BAALC) is a protein that controls leukemia cell proliferation, differentiation, and survival and is overexpressed in several cancer types. The gene is located in the chromosomal region 8q22.3, an area commonly amplified in breast cancer and associated with poor prognosis. However, the expression and potential role of BAALC in breast cancer has not widely been examined. This study investigates BAALC expression in human breast cancers with the aim of determining if it plays a role in the pathogenesis of the disease. BAALC protein expression was examined by immunohistochemistry in breast cancer, and matched lymph node and normal breast tissue samples. The effect of gene expression on overall survival (OS), disease-free and distant metastasis free survival (DMFS) was assessed in silico using the Kaplan-Meier Plotter (n=3,935), the TCGA invasive breast carcinoma (n=960) and GOBO (n=821) data sets. Functional effects of BAALC expression on breast cancer proliferation, migration and invasion were determined in vitro. We demonstrate herein that BAALC expression is progressively increased in primary and breast cancer metastases when compared to normal breast tissue. Increased BAALC mRNA is associated with a reduction in DMFS and disease-free survival, but not OS, in breast cancer patients, even when corrected for tumor grade. We show that overexpression of BAALC in MCF-7 breast cancer cells increases the proliferation, anchorage-independent growth, invasion, and migration capacity of these cells. Conversely, siRNA knockdown of BAALC expression in Hs578T breast cancer cells decreases proliferation, invasion and migration. We identify that this BAALC associated migration and invasion is mediated by focal adhesion kinase (FAK)-dependent signaling and is accompanied by an increase in matrix metalloproteinase (MMP)-9 but not MMP-2 activity in vitro. Our data demonstrate a novel function for BAALC in the control of breast cancer metastasis, offering a potential target for the generation of anti-cancer drugs to prevent breast cancer metastasis.

scholarly journals Silencing of Sphingosine 1-Phosphate Receptors and Potassium Channels May Inhibits the Invasion and Migration of Breast Cancer

2021 ◽  
Author(s):  
Didem Turgut Cosan ◽  
Ahu SOYOCAK ◽  
İbrahim Uğur ÇALIŞ
Keyword(s):  
Breast Cancer ◽  
Potassium Channels ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Mcf 7

Abstract Molecular receptor signaling mechanisms play an important role in many pathophysiological processes, including breast cancer. The spread of cancer from peripheral tissue to distant organs by metastasis is the cause of death of most breast cancer patients. For that reason, the most important step in the treatment of cancer is to prevent metastasis. Sphingosine-1-phosphate receptors and potassium channels play role of cancer cell migration, invasion and they may interact with each other in the progression of cancer. In this study, it was aimed to determine the effects of combined silencing of receptors and channels on the invasion and migration of MCF-7 and MDA-MB-231 breast cancer cells and their interactions on cells. We examined the expression levels of S1P1, S1P3, Kv1.3, and Kv10.1 in MCF-7 and MDA-MB-231 breast cancer cell lines by qRT-PCR. The effects of migration and invasion of breast cancer cells were determined through invasian and wound healing assays. It was observed that high invasion and lateral motility in cells decreased with the combined silencing of S1P1, S1P3, Kv1.3 and Kv10.1 in both cell types. It has been determined that silencing the receptors and channels together is more effective than silencing individually. Our data demonstrated the roles of S1P receptors and potassium channels were associated with invasion and migration signaling pathway. Therefore, these are might be possible therapeutic target for breast cancer metastasis.

Melatonin down-regulates microRNA-10a and decreases invasion and migration of triple-negative breast cancer cells

2019 ◽  
Vol 2 (2) ◽  
pp. 86-99
Author(s):  
Jessica Gisleine de Oliveira ◽  
Jéssica Helena de Mora Marques ◽  
Jéssica Zani Lacerda ◽  
Lívia Carvalho Ferreira ◽  
Marcelo Mafra Campos Coelho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Viability ◽  
Cancer Metastasis ◽  
Gene Expression Regulation ◽  
Mirna Sequence ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
E Cadherin

Breast cancer metastasis is one of the main factors associated with high mortality rates among patients. MicroRNAs (miRNAs) play an important role in gene expression regulation, and are associated with the metastatic process in breast cancer. Melatonin, a hormone secreted mainly in the pineal gland, has several oncostatic effects. The aim of this study was to investigate the action of melatonin in the modulation of miRNA-10a-5p and its association with metastatic mechanisms. We have evaluated the effects of melatonin on cell viability in MDA-MB-468 cell line after 24 hours of treatment. MDA-MB-468 and MDA-MB-231 cells were either transfected with inhibitor of miR-10a, or received a scrambled miRNA sequence as a negative control, then these cells were treated with or without melatonin. Gene expression of miR-10a was verified by real-time PCR. Invasion and migration assay using matrigel inserts were performed. The protein expression was analyzed by western blotting to quantify the epithelial-mesenchymal transition (EMT) markers (E-cadherin, claudin 7, and vimentin) and proliferation marker (PIK3CA). Our results showed that melatonin (1 mM) significantly decreased cell viability, and also affected miR-10a expression, which suppressed cell invasion and migration. Melatonin reduced vimentin and claudin 7 protein expressions, and increased E-cadherin. In contrast, inhibition of miR-10a reduced vimentin and did not modulate claudin 7 and E-cadherin. In conclusion, we demonstrated the effectiveness of melatonin in decreasing miR-10a, affecting invasion and migration, and proteins involved with the EMT process, which supports its potential role in the regulation of metastasis.  

scholarly journals Elevated MYO10 Predicts Poor Prognosis and its Deletion Hampers Proliferation and Migration Potentials of Cells Through Rewiring PI3K/Akt Signaling in Cervical Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382093677
Author(s):  
Jian-Hui He ◽  
Jian-Guo Chen ◽  
Bin Zhang ◽  
Jing Chen ◽  
Ke-Li You ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Messenger Rna ◽  
Poor Prognosis ◽  
Akt Signaling ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues

MYO10, recognized as an important regulator of cytoskeleton remodeling, has been reported to be associated with tumorigenesis. However, its functional implication in cervical cancer and potential mechanism still remain to be undetermined currently. MYO10 level in cervical cancer tissues was analyzed by using data retrieved from The Cancer Genome Atlas and ONCOMINE databases. Messenger RNA and protein expression levels were determined by quantitative real-time polymerase chain reaction and Western blotting. Small-interfering RNA and overexpressing plasmid were used for MYO10 silencing and overexpression, and cell proliferation was analyzed by CCK-8. Transwell assays were performed to investigate the ability of cell migration and invasion. MYO10 was upregulated in cervical cancer tissues and cells when compared to normal controls, and survival analysis showed patients with high MYO10 expression had worse overall survival. Moreover, knockdown/overexpression of MYO10 significantly inhibited/enhanced the proliferation, invasion, and migration capabilities of cervical cells transfected with siRNAs/overexpressing plasmid. Additionally, MYO10 silencing inhibited PI3K/Akt signaling pathway by decreasing the phosphorylation status of PI3K and AKT. Data from the present study indicated that MYO10 were overexpressed in patients with cervical cancer and positively linked with poor prognosis. Experimental results suggested that MYO10 induced a significant encouraging effect in cervical cancer cell proliferation, invasion, and migration, linked with involvement of PI3K/Akt signaling. Collectively, these results emphasize a novel role for MYO10 overexpression in cervical cancer and provide a potent therapeutic strategy against cervical cancer.

scholarly journals High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Yang ◽  
Mingjun Ma ◽  
Sihui Yu ◽  
Xi Li ◽  
Jiawen Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Mtorc1 Signaling ◽  
Cervical Cancer Cells ◽  
And Migration

Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is frequently lost in breast cancer samples and is considered as a tumor suppressor. The roles and mechanisms of PAMR1 in other types of cancers are still unclear. In our present study, we identified PAMR1 as an invasion-related regulator in cervical cancer. Public database and immunohistochemical (IHC) analysis showed that the expression level of PAMR1 in cervical cancer tissues was lower than that in normal cervix tissues and was negatively related to clinicopathologic features. The high expression of PAMR1 also predicted a better prognosis of cervical cancer patients. CCK8, Transwell, and wound-healing assays demonstrated that knockdown of PAMR1 facilitated the proliferation, migration, and invasion of cervical cancer cells. Additionally, gene set enrichment analysis (GSEA) showed a variety of cancer-related pathways potentially activated or suppressed by PAMR1. Moreover, we verified that PAMR1 inhibited MYC target and mTORC1 signaling pathways. In conclusion, our study revealed the suppressor role of PAMR1 in cervical cancer, providing a new insight into the molecular mechanism of cervical cancer progression.

miR-3614-3p suppresses cell aggressiveness of human breast cancer by targeting AKT3 and HDAC1 expression

2021 ◽  
Vol 2 (3) ◽  
Author(s):  
Zhenzhen Wang ◽  
◽  
Xintao Jing ◽  
Zhenghao Zhao ◽  
Fang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transwell Migration Assay ◽  
Migration Assay ◽  
Invasion And Migration ◽  
Protein Levels ◽  
And Migration ◽  
Mcf 7

Purpose: MicroRNAs (miRNA) have been reported in the regulation of various pathobiological progression in cancer. Our recent study has reported that miR-3614-3p significantly suppressed the proliferation of Breast Cancer (BC) cells through the downregulation its host gene TRIM25. However, the other functional role of miR3614-3p migration and invasion in BC and its mechanism have not been investigated thoroughly. Materials and methods: The MDA-MB-231 and MCF-7 BC cell lines were purchased. The cell line expression levels of miR-3614- 3p and AKT3/HDAC1 were determined by quantitative real-time PCR (qPCR). The wound healing assay and transwell migration assay were determined. We next measured protein levels of AKT3/HDAC1 by Western blot. Finally, we investigated the role of AKT3/HDAC1 using siRNA; and confirmed the targeting of 3’UTR of AKT3 and HDAC1 through miR-3614-3p using a luciferase reporter assay. Results: In the present research, we studied that overexpression of miR-3614-3p markedly suppressed tumor cell invasion and migration independent TRIM25, whereas through regulated another targets AKT3 and HDAC1 expression. Notably, TRIM25 is also a target gene of miR-3614 which bind to pri-miR-3614 caused TRIM25 silence. Conclusion: miR-3614-3p is an anti-oncogene that can suppress breast cancer cell aggressiveness by targeting AKT3 and HDAC1, which reveals the potential values of miR-3614-3p for suppression of metastasis of BC. Keywords: Breast cancer; miR-3614; AKT3; HDAC1.

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