TGFB2-AS1 inhibits triple-negative breast cancer progression via interaction with SMARCA4 and regulating its targetsTGFB2andSOX2

Abstract

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype for its high rates of relapse, great metastatic potential, and short overall survival. How cancer cells acquire metastatic potency through the conversion of noncancer stem-like cells into cancer cells with stem-cell properties is poorly understood. Here, we identified the long noncoding RNA (lncRNA) TGFB2-AS1 as an important regulator of the reversibility and plasticity of noncancer stem cell populations in TNBC. We revealed that TGFB2-AS1 impairs the breast cancer stem-like cell (BCSC) traits of TNBC cells in vitro and dramatically decreases tumorigenic frequency and lung metastasis in vivo. Mechanistically, TGFB2-AS1 interacts with SMARCA4, a core subunit of the SWI/SNF chromatin remodeling complex, and results in transcriptional repression of its target genes including TGFB2 and SOX2 in an in cis or in trans way, leading to inhibition of transforming growth factor β (TGFβ) signaling and BCSC characteristics. In line with this, TGFB2-AS1 overexpression in an orthotopic TNBC mouse model remarkably abrogates the enhancement of tumor growth and lung metastasis endowed by TGFβ2. Furthermore, combined prognosis analysis of TGFB2-AS1 and TGFβ2 in TNBC patients shows that high TGFB2-AS1 and low TGFβ2 levels are correlated with better outcome. These findings demonstrate a key role of TGFB2-AS1 in inhibiting disease progression of TNBC based on switching the cancer cell fate of TNBC and also shed light on the treatment of TNBC patients.

LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis

“…In addition, a recent study reported that SMARCA4 interacts with lncRNA TGFB2-AS1 and regulates the transcription of its target genes. 38 We next asked whether SMARCA4 involves the effect of PSMB8-AS1 on VCAM1 and ICAM1 expression. However, RNA pulldown assays revealed no interaction between PSMB8-AS1 and SMARCA4 (Figure S20A).…”

Erythrocyte membrane-camouflaged DNA-functionalized upconversion nanoparticles for tumor-targeted chemotherapy and immunotherapy

“…CD44 + CD24 − cells with stem cell-like features are the most common cell type in breast cancer, 49 which is associated with tumor recurrence, metastasis and drug resistance. 50 The CD44 antigen is a multifunctional transmembrane glycoprotein associated with cell adhesion, activation, migration and differentiation and is considered a promising tumor marker.…”

“…48 These findings supported the notion that the camouflaging RBCm coating on these nanoparticles can reduce self-recognition and clearance by the RES and prolong their half-life in circulation in vivo. 42 3.4 In vitro cytotoxicity of HR@UCNPs/CpG-Apt/DOX CD44 + CD24 − cells with stem cell-like features are the most common cell type in breast cancer, 49 which is associated with tumor recurrence, metastasis and drug resistance. 50 The CD44 antigen is a multifunctional transmembrane glycoprotein associated with cell adhesion, activation, migration and differentiation and is considered a promising tumor marker.…”

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

“…SOX-2 has demonstrated the potential to be a clinically useful biomarker to maintain lung CSCs [ 33 ]. There are also studies in the literature reporting that SOX-2 is overexpressed and acts as an oncogene in lung cancer [ 68 , 69 ]. Although the role of SOX-2 in lung cancer has been determined as a result of clinical and preclinical studies [ 70 ].…”