RESUMEN
SWI/SNF chromatin remodeling complexes play a key role in gene transcription as epigenetic regulators and are typically considered to act as tumor suppressors in cancers. Compared to other cancer-related components of the SWI/SNF complex, research on SMARCC2, a component of the initial BAF core, has been relatively limited. This study aimed to elucidate the role of SMARCC2 in breast cancer by employing various in vitro and in vivo methods including cell proliferation assays, mammosphere formation, and xenograft models, complemented by RNA-seq, ATAC-seq, and ChIP analyses. The results showed that SMARCC2 silencing surprisingly led to the suppression of breast tumorigenesis, indicating a pro-tumorigenic function for SMARCC2 in breast cancer, which contrasts with the roles of other SWI/SNF subunits. In addition, SMARCC2 depletion reduces cancer stem cell features of breast cancer cells. Mechanistic study showed that SMARCC2 silencing downregulated the oncogenic Ras-PI3K signaling pathway, likely by directly regulating the chromatin accessibility of the enhancers of the key genes such as PIK3CB. Together, these results expand our understanding of the SWI/SNF complex's role in cancer development and identify SMARCC2 as a promising new target for breast cancer therapies.
Asunto(s)
Neoplasias de la Mama , Cromatina , Silenciador del Gen , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Cromatina/metabolismo , Cromatina/genética , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Ratones , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proliferación Celular/genética , Carcinogénesis/genética , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Transducción de Señal , Ratones Desnudos , Ensamble y Desensamble de Cromatina/genéticaRESUMEN
Long non-coding RNAs (lncRNAs) have been found to play essential roles in the cell proliferation, fission and differentiation, involving various processes in humans. Recently, there is more and more interest in exploring the relationship between lncRNAs and tumors. Many latest evidences revealed that LINC00467, an oncogenic lncRNA, is highly expressed in lung cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, breast cancer, glioblastoma, head and neck squamous cell carcinoma, osteosarcoma, and other malignant tumors. Besides, LINC00467 expression was linked with proliferation, migration, invasion and apoptosis via the regulation of target genes and multiple potential pathways. We reviewed the existing data on the expression, downstream targets, molecular mechanisms, functions, relevant signaling pathways, and clinical implications of LINC00467 in various cancers. LINC00467 may serve as a novel biomarker or therapeutic target for the diagnosis and prognosis of various human tumors.
RESUMEN
The Hippo signaling pathway was found coordinately modulates cell regeneration and organ size. Its dysregulation contributes to uncontrolled cell proliferation and malignant transformation. YAP/TAZ are two critical effectors of the Hippo pathway and have been demonstrated essential for the initiation or growth of most tumors. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, have been shown to play critical roles in the development of many cancers. In the past few decades, a growing number of studies have revealed that ncRNAs can directly or indirectly regulate YAP/TAZ signaling. YAP/TAZ also regulate ncRNAs expression in return. This review summarizes the interactions between YAP/TAZ signaling and noncoding RNAs together with their biological functions on cancer progression. We also try to describe the complex feedback loop existing between these components.
Asunto(s)
MicroARNs , Neoplasias , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Humanos , MicroARNs/genética , Neoplasias/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAPRESUMEN
Long non-coding RNAs (lncRNAs) are important regulators and biomarkers of tumorigenesis and tumor metastasis. Long intergenic non-protein-coding RNA 467 (LINC00467) is associated with various cancers. However, the role and mechanism of LINC00467 in colorectal cancer (CRC) promotion are poorly understood. This study aimed to present new details of LINC00467 in the progression of CRC. Reverse transcription-polymerase chain reaction demonstrated that the expression level of LINC00467 in CRC tissues and cell lines was significantly upregulated, which was closely related to the clinical features of CRC. Cell and animal studies showed that the downregulation of LINC00467 expression in CRC cells significantly inhibited cell proliferation, metastasis, and angiogenesis. Moreover, the overexpression of LINC00467 accelerated CRC promotion. Bioinformatics analysis and luciferase reporter assay confirmed that LINC00467 binds to miR-128-3p. Rescue experiments manifested that decreased miR-128-3p level reversed CRC cell inhibition by silencing LINC00467. Furthermore, vascular endothelial growth factor C (VEGFC) was identified as a target of miR-128-3p that could reverse the inhibition of cell growth that is mediated by miR-128-3p. Altogether, our results showed that LINC00467 contributes to CRC progression and angiogenesis via the miR-128-3p/VEGFC axis. Our findings expand the understanding of the mechanisms underlying CRC and suggest potential targets for clinical strategies against CRC.
Asunto(s)
Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Animales , Proliferación Celular/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factor C de Crecimiento Endotelial Vascular/genética , Factor C de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Long non-coding RNAs (lncRNAs) are non-coding RNAs that have more than 200 nucleotides and can participate in the regulation of gene expression in various ways. An increasing number of studies have shown that the dysregulated expression of lncRNAs is related to the occurrence and progression of human cancers. LINC00665 is a novel lncRNA, which is abnormally expressed in various human cancers, such as lung cancer, breast cancer, prostate cancer, and glioma. LINC00665 functions in many biological processes of tumor cells, such as cell proliferation, migration, invasion, angiogenesis, and metabolism, and is related to the clinicopathological characteristics of cancer patients. LINC00665 can play biological functions as a ceRNA, directly binding and interacting with proteins, and as an upstream molecule regulating multiple signaling pathways. In this review, we comprehensively summarize the expression level, function, and molecular mechanisms of LINC00665 in different human cancers and emphasize that LINC00665 is a promising new diagnostic, prognostic biomarker, and therapeutic target.