MALAT-1: LncRNA ruling miR-182/PIG-C/mesothelin triad in triple negative breast cancer

Barsoum, Farida S.; Awad, Amany; Hussein, Nada H.; Eissa, Reda A.; Tayebi, H.M. El

doi:10.1016/j.prp.2020.153274

Cited by 10 publications

(13 citation statements)

References 48 publications

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“…MALAT1 was found to be over expressed in hormonal, HER2+, and TNBC compared to controls, as shown in Figure 1A . This finding aligns with our previous studies confirming that MALAT1 is overexpressed in BC tissues more than healthy tissues ( Barsoum et al, 2020 ). Nevertheless, another research study observed the overexpression of MALAT1 in many BC cell lines (MCF-7, SK-BR-3, MDA-MB-468, MDA-MB-231, T-47d, and MDA-MB-453) compared to normal breast epithelial cell line (MCF-10A) ( Yue et al, 2020 ).…”

Section: Discussionsupporting

confidence: 93%

“…In our previous work, MALAT1 was shown to be upregulated in BC tissues, especially TNBC epigenetically upregulating MSLN; Barsoum et al (2020 ) proposed that there may be a possible interlinkage between MALAT1 and immunomodulatory proteins. The aim of the current study is to investigate if MALAT1 will give the same pattern of expression in TAMs of the hormonal, HER2+, and TNBC, highlighting that its role in cancer is still controversial whether it is an oncogenic or a tumor suppressor lncRNA.…”

Section: Discussionmentioning

confidence: 97%

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A cutting-edge immunomodulatory interlinkage between HOTAIR and MALAT1 in tumor-associated macrophages in breast cancer: A personalized immunotherapeutic approach

Amer

Eissa²,

Tayebi³

2022

Front. Mol. Biosci.

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Breast cancer (BC) is one of the most common cancers, accounting for 2.3 million cases worldwide. BC can be molecularly subclassified into luminal A, luminal B HER2-, luminal B HER2+, HER2+, and triple-negative breast cancer (TNBC). These molecular subtypes differ in their prognosis and treatment strategies; thus, understanding the tumor microenvironment (TME) of BC could lead to new potential treatment strategies. The TME hosts a population of cells that act as antitumorigenic such as tumor-associated eosinophils or pro-tumorigenic such as cancer-associated fibroblasts (CAFs), tumor-associated neutrophils (TANs), monocytic-derived populations such as MDSCs, or most importantly “tumor-associated macrophages (TAMs),” which are derived from CD14+ monocytes. TAMs are reported to have the pro-inflammatory phenotype M1, which is found only in the very early stages of tumor and is not correlated with progression; however, the M2 phenotype is anti-inflammatory that is correlated with tumor progression and metastasis. The current study focused on controlling the anti-inflammatory activity in TAMs of hormonal, HER2+, and TNBC by epigenetic fine-tuning of two immunomodulatory proteins, namely, CD80 and mesothelin (MSLN), which are known to be overexpressed in BC with pro-tumorigenic activity. Long non-coding RNAs are crucial key players in tumor progression whether acting as oncogenic or tumor suppressors. We focused on the regulatory role of MALAT1 and HOTAIR lncRNAs and their role in controlling the tumorigenic activity of TAMs. This study observed the impact of manipulation of MALAT1 and HOTAIR on the expression of both CD80 and MSLN in TAMs of BC. Moreover, we analyzed the interlinkage between HOTAIR and MALAT1 as regulators to one another in TAMs of BC. The current study reported an upstream regulatory effect of HOTAIR on MALAT1. Moreover, our results showed a promising use of MALAT1 and HOTAIR in regulating oncogenic immune-modulatory proteins MSLN and CD80 in TAMs of HER2+ and TNBC. The downregulation of MALAT1 and HOTAIR resulted in the upregulation of CD80 and MSLN, which indicates that they might have a cell-specific activity in TAMs. These data shed light on novel key players affecting the anti-inflammatory activity of TAMs as a possible therapeutic target in HER2+ and TNBC.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 97%

A cutting-edge immunomodulatory interlinkage between HOTAIR and MALAT1 in tumor-associated macrophages in breast cancer: A personalized immunotherapeutic approach

Amer

Eissa²,

Tayebi³

2022

Front. Mol. Biosci.

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“…Meanwhile, miR-182-5p could promote the proliferation, migration and angiogenesis of HUVECs. Consistently, the expression of miR-182 has shown a dramatic overexpression in breast cancer tissue samples (Barsoum et al 2020 ), and moreover, its overexpression significantly relates to poor clinical and pathological tumor characteristics in patients with locally advanced triple negative breast cancer and thus can be used as a tool to predict the outcomes and prognosis in these patients (Bajaj 2020 ). Downregulation of miR-182-5p contributes to inhibition of cell proliferation and promotion of tumor cell apoptosis by impairing the TLR4/NF-κB signaling pathway activity and increasing FBXW7 expression (Wu et al 2020 ).…”

Section: Discussionmentioning

confidence: 88%

Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis

Zhao

Wang

et al. 2021

Mol Med

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Background Extracellular vesicles (EVs) derived from tumor cells are implicated in the progression of malignancies through the transfer of molecular cargo microRNAs (miRNAs or miRs). We aimed to explore the role of EVs derived from breast cancer cells carrying miR-182-5p in the occurrence and development of breast cancer. Methods Differentially expressed miRNAs and their downstream target genes related to breast cancer were screened through GEO and TCGA databases. miR-182-5p expression was examined in cancer tissues and adjacent normal tissues from patients with breast cancer. EVs were isolated from breast cancer cell line MDA-MB-231 cells and identified. The gain- and loss-of function approaches of miR-182-5p and CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) were performed in MDA-MB-231 cells and the isolated EVs. Human umbilical vein endothelial cells (HUVECs) were subjected to co-culture with MDA-MB-231 cell-derived EVs and biological behaviors were detected by CCK-8 assay, flow cytometry, immunohistochemical staining, Transwell assay and vessel-like tube formation in vitro. A xenograft mouse model in nude mice was established to observe the tumorigenesis and metastasis of breast cancer cells in vivo. Results miR-182-5p was highly expressed in breast cancer tissues and cells, and this high expression was associated with poor prognosis of breast cancer patients. miR-182-5p overexpression was shown to promote tumor angiogenesis in breast cancer. Moreover, our data indicated that miR-182-5p was highly enriched in EVs from MDA-MD-231 cells and then ultimately enhanced the proliferation, migration, and angiogenesis of HUVECs in vitro and in vivo. Moreover, we found that CMTM7 is a target of miR-182-5p. EVs-miR-182-5p promotes tumorigenesis and metastasis of breast cancer cells by regulating the CMTM7/EGFR/AKT signaling axis. Conclusions Taken altogether, our findings demonstrates that EVs secreted by breast cancer cells could carry miR-182-5p to aggravate breast cancer through downregulating CMTM7 expression and activating the EGFR/AKT signaling pathway.

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“…Tumor-associated antigen-mesothelin (MSLN) is a glycoprotein that exists on the cell surface and is highly expressed in various tumor tissues such as mesothelioma, non-small cell lung cancer, pancreatic cancer, and metastatic triple negative breast cancer, while no longer expressed in normal tissues or is low expressed in mesothelial tissues ( 74 ). Due to the characteristic of MSLN, it has become the focus of specific targeting antigen of tumor cells.…”

Section: Potential Therapeutic Directions and Possible Strategiesmentioning

confidence: 99%

Prospects of Immunotherapy for Triple-Negative Breast Cancer

et al. 2022

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In the classification and typing of breast cancer, triple-negative breast cancer (TNBC) is one type of refractory breast cancer, while chemotherapy stays in the traditional treatment methods. However, the impact of chemotherapy is short-lived and may lead to recurrence due to incomplete killing of tumor cells. The occurrence, development, and relapse of breast cancer are relevant to T cell dysfunction, multiplied expression of related immune checkpoint molecules (ICIs) such as programmed death receptor 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) produce immunosuppressive effect. Immunotherapy (namely, immune checkpoint inhibitors, adoptive cellular immunotherapy, CAR-T immunotherapy and some potential treatments) provides new hope in TNBC. This review focuses on the new immune strategies of TNBC patients.

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MALAT-1: LncRNA ruling miR-182/PIG-C/mesothelin triad in triple negative breast cancer

Cited by 10 publications

References 48 publications

A cutting-edge immunomodulatory interlinkage between HOTAIR and MALAT1 in tumor-associated macrophages in breast cancer: A personalized immunotherapeutic approach

A cutting-edge immunomodulatory interlinkage between HOTAIR and MALAT1 in tumor-associated macrophages in breast cancer: A personalized immunotherapeutic approach

Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis

Prospects of Immunotherapy for Triple-Negative Breast Cancer

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