LINC00173 facilitates tumor progression by stimulating RAB1B‐mediated PA2G4 and SDF4 secretion in nasopharyngeal carcinoma

• Published in: Molecular oncology Vol. 17; no. 3; pp. 518 - 533
• Main Authors: He, Shi‐Wei, Liang, Ye‐Lin, Zhang, Yuan, Liu, Xu, Gong, Sha, Ye, Ming‐Liang, Huang, Sheng‐Yan, Tan, Xi‐Rong, Zhou, Shi‐Qing, Zhao, Yin, Liu, Na, Li, Ying‐Qing
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2023; John Wiley and Sons Inc; Wiley
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Antibodies; Biotechnology; Calcium-binding protein; Calcium-Binding Proteins - genetics; Cancer therapies; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; Cloning; Cytoplasm; Gene Expression Regulation, Neoplastic; Glycoproteins - genetics; Humans; LINC00173; Lymph nodes; Mass spectrometry; Medical prognosis; Metastases; Metastasis; mRNA; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Non-coding RNA; Ontology; PA2G4; Phenotypes; Plasmids; Proteins; rab1 GTP-Binding Proteins - genetics; rab1 GTP-Binding Proteins - metabolism; RAB1B; Reagents; Review boards; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-Binding Proteins - metabolism; Scientific imaging; SDF4; Secretion; Therapeutic targets; Tumors; Beijing China; Grand Island New York; United States > US; China; SDF4; nasopharyngeal carcinoma; PA2G4; RAB1B; LINC00173
• ISSN: 1574-7891; 1878-0261; 1878-0261
• DOI: 10.1002/1878-0261.13375

An increasing number of studies have found that long non‐coding RNA (lncRNA) play important roles in driving the progression of nasopharyngeal carcinoma (NPC). Our microarray screening revealed that expression of the lncRNA long intergenic non‐protein coding RNA 173 (LINC00173) was upregulated in NPC. However, its role and mechanism in NPC have not yet been elucidated. In this study, we demonstrate that high LINC00173 expression indicated a poor prognosis in NPC patients. Knockdown of LINC00173 significantly inhibited NPC cell proliferation, migration and invasion in vitro. Mechanistically, LINC00173 interacted and colocalized with Ras‐related protein Rab‐1B (RAB1B) in the cytoplasm, but the modulation of LINC00173 expression did not affect the expression of RAB1B at either the mRNA or protein levels. Instead, relying on the stimulation of RAB1B, LINC00173 could facilitate the extracellular secretion of proliferation‐associated 2G4 (PA2G4) and stromal cell‐derived factor 4 (SDF4; also known as 45‐kDa calcium‐binding protein) proteins, and knockdown of these proteins could reverse the NPC aggressive phenotype induced by LINC00173 overexpression. Moreover, in vivo LINC00173‐knockdown models exhibited a marked slowdown in tumor growth and a significant reduction in lymph node and lung metastases. In summary, LINC00173 serves as a crucial driver for NPC progression, and the LINC00173–RAB1B–PA2G4/SDF4 axis might provide a potential therapeutic target for NPC patients. Our study shows that LINC00173 is upregulated in nasopharyngeal carcinoma (NPC) and is associated with poor prognosis of patients. LINC00173 directly binds and interacts with RAB1B, subsequently facilitates PA2G4 and SDF4 secretion through exocytosis pathway, finally, promotes NPC cell proliferation, migration, invasion and metastasis. The LINC00173–RAB1B–PA2G4/SDF4 axis might provide a potential therapeutic target for NPC patients.