Downregulation of long non-coding RNA MALAT1 induces tumor progression of human breast cancer through regulating CCND1 expression

AbstractObjectiveMetastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is already known to be involved in the development and progression of many types of tumors. In the present study, we set to seek the role of MALAT1and the molecular mechanisms in breast cancer.MethodsMALAT1 mRNA expression level was measured by real-time PCR in selected tissues and breast cancer cell lines. SiRNAs targeting MALAT1 were employed to knockdown the endogenous MALAT1. Then cell counting method and colony formation method were applied to reveal the proliferation changes after MALAT1 was suppressed. Afterwards, the mRNA and protein expression of growth related gene cyclinD1 (CCND1) were detected by RT-PCR and western blotting, respectively.ResultsWe found a downregulation of MALAT1 expression in breast cancer cell lines and tissues. Inhibition of its expression led to enhanced cell proliferation and colony formation. Importantly, the mRNA and protein expression of CCND1 was significantly increased in MALAT1-depleted cells.ConclusionMALAT1 is a potential tumor suppressive long non-coding RNA that negatively regulates cell proliferation in breast cancer progression, via suppressing CCND1 expression.

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Dexamethasone Downregulates BCRP mRNA and Protein Expression in Breast Cancer Cell Lines

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504009789745674 ◽

2009 ◽

Vol 18 (1) ◽

pp. 9-15 ◽

Cited By ~ 18

Author(s):

Fatemeh Elahian ◽

Fatemeh Kalalinia ◽

Javad Behravan

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Mrna And Protein Expression

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O25 Expression of polymeric immunoglobulin receptor (PIGR) and the effect of PIGR overexpression on breast cancer cells

British Journal of Surgery ◽

10.1093/bjs/znab282.030 ◽

2021 ◽

Vol 108 (Supplement_5) ◽

Author(s):

W Asanprakit ◽

D N Lobo ◽

O Eremin ◽

A J Bennett

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Cell Lines ◽

Breast Cancer Cell ◽

Favourable Outcome ◽

Breast Cancer Cell Lines ◽

Polymeric Immunoglobulin Receptor ◽

Immunoglobulin Receptor ◽

Transfected Cells ◽

Mrna And Protein Expression

Abstract Introduction Polymeric immunoglobulin receptor (PIGR) has a major role in mucosal immunity as a transporter of polymeric immunoglobulin across the epithelial cells. PIGR expression increases in various cancers and relates to patient outcomes. Functional roles of PIGR have been explored in several cancers such as hepatocellular, pancreatic and lung cancer. The aim of this study was to determine the effect of PIGR on cellular behaviours and chemo-sensitivity of MCF7 and MDA-MB468 breast cancer cell lines. Method Basal levels of PIGR mRNA and protein expression in MCF7 and MDA-MB468 cells were evaluated by real time quantitative polymerase chain reaction and Western blotting, respectively. MCF7/PIGR and MDA-MB468/PIGR stable cell lines, overexpressing the PIGR gene, were generated using a lentiviral vector with tetracycline dependent induction of expression. Cell viability, cell proliferation and chemo-sensitivity of PIGR transfected cells were evaluated and compared with un-transfected cells to determine the effect of PIGR overexpression on cell phenotype. Result The levels of PIGR mRNA and protein expression were significantly higher in MDA-MB468 cells than in MCF7 cells (380-fold, P < 0.0001). However, the differential expression of PIGR in these two cell lines did not lead to significant differences in chemo-sensitivity. Viral overexpression of PIGR was also not found to change any of the parameters measured in either cell line. Conclusion PIGR per se does not affect cellular behaviours and chemo-sensitivity of these breast cancer cell lines. It may be a marker which works through other factors rather than being a direct contributor of the favourable outcome in patients. Take-home Message PIGR may be a marker of favourable outcome in breast cancer patients which works through other factors rather than being a direct contributor.

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MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

International Journal of Molecular Sciences ◽

10.3390/ijms22105382 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5382

Author(s):

Pei-Yi Chu ◽

Hsing-Ju Wu ◽

Shin-Mae Wang ◽

Po-Ming Chen ◽

Feng-Yao Tang ◽

...

Keyword(s):

Breast Cancer ◽

Survival Rate ◽

Protein Expression ◽

Cancer Patients ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Breast Cancer Patients ◽

Expression Ratio

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan–Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.

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Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

Scientific Reports ◽

10.1038/s41598-020-80152-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tiantian Tang ◽

Guiying Wang ◽

Sihua Liu ◽

Zhaoxue Zhang ◽

Chen Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

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Integrative analysis of mRNA and miRNA proﬁles identifies miR-193 and miR-210 as potential regulatory biomarkers in diﬀerent molecular subtypes of breast cancer

10.21203/rs.3.rs-47634/v1 ◽

2020 ◽

Author(s):

Adriane Feijo Evangelista ◽

Renato J Oliveira ◽

Viviane A O Silva ◽

Rene A D C Vieira ◽

Rui M Reis ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Line ◽

Cell Lines ◽

Breast Cancer Cell ◽

Cancer Progression ◽

Triple Negative ◽

Molecular Subtypes ◽

Breast Cancer Cell Lines ◽

Mcf 7

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.

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