LINC00511 drives invasive behavior in hepatocellular carcinoma by regulating exosome secretion and invadopodia formation

Abstract

Background Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. Methods The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. Results We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Conclusions Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression.

Construction and Validation of Immune-Related LncRNA Signature to Predict the Prognosis and Therapeutic Efficacy of Breast Cancer

“…For example, LINC00511 may contribute to breast cancer tumorigenesis, proliferation, radioresistance, and stemness 20,21 . The tumor-promoting functions of LINC00511 have also been reported in gastric cancer 22,23 , hepatocellular carcinoma 24,25 , colorectal cancer 26, 27 and bladder cancer 28,29 . LINC01087 could represent a novel, speci c and promising biomarker not only for the diagnosis and prognosis of luminal subtypes and triple-negative breast cancers but also as a predictive biomarker of pharmacological interventions 30 .…”

Molecular Classification of Breast Cancer Utilizing Long Non-Coding RNA (lncRNA) Transcriptomes Identifies Novel Diagnostic lncRNA Panel for Triple-Negative Breast Cancer

“…In addition to this, the silencing of LINC00511 expression suppressed cell viability, proliferation, migration, and invasion, and accelerated the apoptosis of glioma cells via a suggested miR-15a-5p/AEBP1 axis [ 36 ]. Other studies have associated LINC00511 with breast cancer [ 37 ], hepatocellular carcinoma [ 38 ], and bladder carcinoma [ 39 ].…”

Expression changes of serum LINC00941 and LINC00514 in HBV infection‐related liver diseases and their potential application values

“… 20 Research by Peng et al showed that the expression of LINC00511 was higher in HCC tissues, and the mechanism study revealed that the invasion pseudopodia and exosomal secretion induced by LINC00511 were involved in tumor progression. 21 Yin et al found that LINC01133 expression in HCC tissues was elevated, and can predict the poor prognosis of HCC patients; in‐vitro studies showed that overexpression of LINC01133 can promote the proliferation and aggressive phenotype of HCC cells, and promote tumor growth and lung metastasis in vivo, while knockdown LINC01133 had the opposite effect. 22 In addition, studies have also reported that lncRNA plays an important role in the chemotherapy resistance of HCC.…”