LncRNA TP73‐AS1 promotes nasopharyngeal carcinoma progression through targeting miR-342-3p and M2 polarization via exosomes

Abstract

Background Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms. Methods Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages. Results LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages. Conclusions Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC.

Immune cells-derived exosomes function as a double-edged sword: role in disease progression and their therapeutic applications

“…During this transfer, the rate of proliferation and production of cytokines in non-exhausted TCD8 + cells decreases, and the levels of inhibitory markers such as PD-1 and TIM-3 increase at their surfaces [76,77]. Because lncRNAs are the main factor in this action, exosomes must integrate with the target cell membrane [78].…”

Revealing the crosstalk between nasopharyngeal carcinoma and immune cells in the tumor microenvironment

“…As for NPC-lncRNAs, lncRNA-LINC00460 and lncRNA PVT1 have been involved in glucose metabolism and susceptibility to T cell-mediated lysis of NPC cells [66][67][68]. LncRNA TP73-AS1 is carried from NPC cells by extracellular vesicles and is associated with the polarization of macrophage toward the M2 phenotype [69]. TP73-AS1 is associated with a variety of cancers, so presumably, TP73-AS1 may be an NPC potential target [70][71][72].…”

Tumor-derived extracellular vesicles modulate innate immune responses to affect tumor progression

“…Mechanistically, HMMR-AS1 interacts with miR-147a to reduce ARID3A degradation after which M2 macrophage polarization and the development of HCC are promoted ( 77 ). In addition, lncRNA TP73-AS1 is highly expressed in nasopharyngeal carcinoma cell-derived EVs, which binds to miR-342-3p, promotes the M2 polarization of macrophages, and reinforces the motility and microtubule formation of macrophages ( 78 ). Furthermore, FGD5-AS1 enriched in pancreatic cancer cell-derived EVs mediates M2 polarization of macrophages by activating STAT3/NF-κB pathway ( 79 ).…”