MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression

Abstract

Misregulation of long non-coding RNA (lncRNA) genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin1 (Tns1) to regulate its expression in trans. The Tns1 protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. We identify LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and metastasis. Our findings demonstrate that LINC01271 represents a potential therapeutic target to alter breast cancer progression.

Construction and Analysis of the Dysregulated ceRNA Network and Identification of Risk Long Noncoding RNAs in Breast Cancer

“…Xiao et al (2020) found that the lncRNA MAFG-AS1, which is highly expressed in bladder urothelial carcinoma, is correlated with aggressive characteristics and poor prognosis of bladder urothelial carcinoma. As for BRCA, IRNAS HOTAIR, SPRY4-IT1, GAS5, MATAR25, PANDAR, and MATAR25, new players in tumor development and prognosis, have shown owning potential clinical applications in BRCA (Soudyab et al, 2016;Nagini, 2017;Chang et al, 2020). In addition, viable ways have been considered to predict the potential BRCA lncRNAs by performing highthroughput data based on bioinformatics methods (Guo et al, 2018;Chi et al, 2019;Wang et al, 2019).…”

LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p

“…Recent studies revealed that lncRNAs acted as a key regulator in the pathogenesis, progression, and phenotype development of breast cancer (32). Growing data delineated LncRNAs dysregulated in breast cancer (33)(34)(35)(36)(37). As previously described, lncRNA FGD5-AS1 participated as an essential mediator in various cancer.…”

The Roles of Pseudophosphatases in Disease

“…Considering this special edition focused on the roles of protein tyrosine phosphatases in signaling, with an emphasis on therapeutic strategies, the pseudophosphatases' signaling mechanisms linked to diseases, myotubularins, tensins, and STYX pseudophosphatases, was discussed in more detail. [68] The proteins here all contain alterations in their catalytic active site motifs that are associated with loss of phosphatase function.…”

“…Since tensin 1 and tensin 2 are pseudophosphatases, they will be described in more detail. Knockout mouse studies have linked their functionality to muscle regeneration and to diseases (Figure 4) such as kidney failure, cancer, chronic obstructive pulmonary disease (COPD), etc., [31,64,66,68,94,95]. Tensin 1 is a 220-kD cytoplasmic phosphoprotein localized to focal adhesions, serving as a molecular bridge linking the extracellular matrix (ECM), actin cytoskeleton, and signal transduction [64,66,95,96].…”

“…Recently, tensin 1 has been linked to breast cancer (Figure 4A). Intriguingly, tensin 1 appears to have paradoxical roles in decreasing breast cancer (Figure 4(Aiii)) [68] as well as promoting breast cancer (Figure 4(Aiv)) [68]. As an inhibitor, tensin prevents the Rho GTPase cell division cycle 42 (cdc42) from performing its duties of signaling cells to become invasive and metastasize [68].…”