Abstract
BackgroundAs a type of new targets for prognosis of malignancies, long non-coding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcription 1) is associated with proliferation and metastatic abilities of several malignancies. However, its relations to development and migration of triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers haven't been reported.ObjectivesIn this paper, we aimed to discuss how MALAT1 is connected with and affects proliferation and invasion abilities of cells in Her-2 positive and triple-negative breast cancers (TNBC).MethodsThe expression of MALAT1 in clinical samples with TNBC and Her-2 positive breast cancers was tested by qRT-PCR. The statistical analysis was performed to unveil the potential relationships between the expression of MALAT1 and prognostic factors of breast cancer such as OS (overall survival), RFS (relapse-free survival), number of metastatic lymph nodes and pTNM staging in patients with TNBC or Her-2 positive breast cancer. MALAT1 and XBP1 were knockdown respectively in Her-2 positive cell line MDA-MB-231, and MALAT1 and Her-2 were knockdown respectively in TNBC cell line MDA-MD-435 using siRNA. The alterations of expressions of MALAT1 and related genes were detected by qRT-PCR in two breast cancer cell lines. The changes of proliferation abilities in two cell lines were observed using CCK8 assays. Furthermore, transwell assays were performed to detect changes to invasion abilities of the cells.ResultsThe expression of MALAT1 in triple negative and Her-2 positive breast cancers was positively correlated to the number of metastatic lymph nodes in patients with breast cancer. MALAT1 promotes proliferation and invasion abilities of breast cancer cells through XBP1 (X-box binding protein 1)-HIF (hypoxia-inducible factor)-1α pathway in MDA-MB-231 and through Her-2 pathway in MDA-MD-435. Moreover, MALAT1 could possibly be involved in regulation of MYC gene and CD47 (an immune checkpoint gene) in both cell lines.ConclusionsOur study suggested that MALAT1 is a core signaling molecule for promoting development and migration of triple negative and Her-2 positive breast cancers. It would be employed as common markers for prognosis of the two types of breast cancer mentioned above and potential targets for treating them.
Highlights
Breast cancer is one of the most common malignancies for females, with the highest incidence among female malignancies in China and even around the world [1]
The expression of MALAT1 in triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers was positively correlated to the number of metastatic lymph nodes in patients with breast cancer
Our study suggested that MALAT1 is a core signaling molecule for promoting development and migration of triple negative and Her-2 positive breast cancers
Summary
Breast cancer is one of the most common malignancies for females, with the highest incidence among female malignancies in China and even around the world [1]. Targeted molecular therapies are therapeutic schedules for oncogenes of the disease and related expression products, which aim to improve treatment precision of breast cancer. In 2011, experts reached a consensus at the St Gallen International Breast Cancer Conference that breast cancer should be classified into Luminal A, Luminal B, Her-2 positive and triple negative molecular subtypes, in order to develop pertinent clinical therapeutic regimes [3]. Triple-negative breast cancer (TNBC) and Her-2 positive breast cancer are characterized by higher degree of malignancy, higher invasiveness, faster progression, higher recurrence, distant metastasis, poor prognosis and higher mortality. There are scarcely any effective targets for treating TNBC It is of great significance for further study of molecular mechanisms related to TNBC and Her-2 positive breast cancers, and for the attempt to finding new molecular targets for treating these two kinds of breast cancer. Its relations to development and migration of triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers haven’t been reported
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