Role and Mechanism of Exosome-Derived Long Noncoding RNA HOTAIR in Lung Cancer.

Abstract

Background and purpose: HOX transcript antisense RNA (HOTAIR) is a long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes can mediate intracellular communication in cancer by transferring active molecules. However, the role and mechanism of HOTAIR in nonsmall cell lung cancer (NSCLC) are still unclear. This study mainly explores the role and mechanism of exosome-derived HOTAIR in NSCLC. Methods: after the material characterization of the CD63 immune lipid magnetic bead (CD63-IMB), the exosomes in serum of NSCLC patients were captured through CD63-IMB for the corresponding biological characterization. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression level of HOTAIR in tumor tissues, serum, and serum exosome from NSCLC patients. Subsequently, exosome secreted by NCI-H1975 cells with highly expressed HOTAIR was selected to treat low-expression A549 cells and HOTAIR knockdown on NCI-H1975 cells. In this way, action mechanisms of HOTAIR can be investigated by means of qRT-PCR, colony formation assays, and flow cytometry. Results: exosomes can be isolated by CD63-IMB, and taken up by cells effectively; the qRT-PCR results demonstrate that HOTAIR expressions are significantly upregulated in tumor tissues, serums, and exosomes isolated from serums of NSCLC patients. Clinicopathological correlation analysis shows that the upregulation of HOTAIR is closely associated with lymphatic metastasis and tumor node metastasis (TNM) staging (P < 0.05). HOTAIR expressions show a significant increase in A549 cells treated with exosomes derived from NCI-H1975 cells, signifying that both proliferation and migration of A549 cells are promoted, and HOTAIR depletion could inhibit the proliferation and migration of lung cancer cells. Conclusions: HOTAIR is highly expressed in tumor tissues, serums, and serum exosomes of NSCLC patients and its expression has a significant correlation with lymphatic metastasis and TNM staging. Moreover, the exosome may promote NSCLC proliferation and migration through HOTAIR transportation. Therefore, exosome-derived HOTAIR is expected to be a new molecular marker for NSCLC diagnosis, and exosomal transmission of HOTAIR may provide a new approach to NSCLC diagnosis.