# Extracellular vesicle-associated lncRNA LYPLAL1-DT mediates endothelial-cancer cell communication, promoting small cell lung cancer progression

## TL;DR

This study shows that a specific long non-coding RNA in exosomes helps aggressive lung cancer grow by communicating with blood vessel cells.

## Contribution

The study reveals a new dual role of exosomal lncRNA LYPLAL1-DT in promoting both cancer cell aggression and blood vessel growth in small cell lung cancer.

## Key findings

- Exosomal LYPLAL1-DT is elevated in SCLC patients and promotes tumor aggressiveness.
- LYPLAL1-DT enhances pro-angiogenic behavior in endothelial cells, accelerating SCLC progression.
- LYPLAL1-DT acts as a competing endogenous RNA through multiple regulatory pathways involving miR-204-5p.

## Abstract

Aim: Representing about 15% of lung cancers, small cell lung cancer (SCLC) is an extremely aggressive disease characterized by rapid growth and early spread, leading to dismal clinical outcomes. In this study, we aimed to investigate the dual roles of exosomal long non-coding RNA (lncRNA) LYPLAL1-DT (LYPLAL1 divergent transcript) in both tumor cells and vascular endothelial cells.

Methods: The circulating levels of LYPLAL1-DT were measured using real-time polymerase chain reaction in 13 SCLC patients and 21 normal controls. Exosomes from the supernatant of cell culture medium or serum were extracted through ultracentrifugation and dyed with PKH67 green fluorescent cell linker to identify internalization. Migration and invasion assay, colony formation, Cell Counting Kit-8 (CCK-8), and tube formation assays were used to assess the malignant effects of extracellular RNAs (exRNAs) LYPLAL1-DT in exosomes.

Results: Exosomal LYPLAL1-DT is upregulated in SCLC patients and plays a dual role in promoting tumor cell aggressiveness and enhancing pro-angiogenic behavior in endothelial cells, thereby accelerating SCLC progression. Mechanistically, LYPLAL1-DT functions as a competing endogenous RNA, exerting its effects through the miR-204-5p/profilin-2, miR-204-5p/B-cell lymphoma 2 and miR-204-5p/sirtuin 1 regulatory axes. These pathways underscore the pleiotropic effects of exosomal LYPLAL1-DT and underscore its value as a promising therapeutic target.

Conclusion: In the current study, we investigated the bidirectional communication mediated by exRNA LYPLAL1-DT between SCLC and endothelial cells, while also exploring its potential regulatory targets. This research provides a potential circulating biomarker for the diagnosis, prognosis, and treatment of SCLC.