SCLC is extremely malignant and often metastasizes extensively when diagnosed . Early diagnosis and treatment of SCLC are therefore paramount. In recent years, some progress has been made in the study of the molecular mechanism and treatment of SCLC, but there is still a lack of reliable specific markers in the early diagnosis and treatment of SCLC. The exosome is an extracellular vesicle that can be secreted by almost all cells. It contains complex RNA and protein and is characterized by high concentration, easy enrichment, and stable biological activity. Therefore, exosome has great clinical diagnostic value. Recent studies have shown that exosome-derived lncRNA-mediated intercellular signal transduction plays an important role in the occurrence and development of tumors . In recent years, the ceRNA hypothesis has proved that lncRNA can competitively bind to miRNA to regulate the expression of target genes , which provides important clues for studying the occurrence and development mechanism of tumors as well as new ideas for early diagnosis and treatment of tumors. The regulatory network of ceRNA has been proved to play an important role in tumors such as gastric cancer, liver cancer, and prostate cancer [15–18]. The proposal of the ceRNA hypothesis and its verification in many other cancers have provided a reliable reference for exploring the mechanisms of the ceRNA regulatory network in SCLC.
In this study, the exosome exoRBase database was used to analyze the genetic data of exosomes in the normal population and peripheral blood of SCLC patients. 13 differentially expressed mRNA, 40 differentially expressed lncRNA, and 59 differentially expressed circRNA were screened out. A ceRNA network consisting of 5 mRNA nodes, 5 lncRNA nodes, 7 circRNA nodes, and 41 miRNA nodes was constructed using Cytoscape software. GO annotation enrichment analysis showed that mRNA was mainly enriched in "melanosome", "pigment granule", "late endosome membrane". The KEGG enrichment analysis showed that the mRNA differentially expressed in the regulatory network were mainly enriched in "Non-small cell lung cancer", "Leucocyte transendothelial migration r", "cell sentinel", "Rap1 signaling pathway", Among them, the most important differential gene RASSF3 was enriched in the "Non-small cell lung cancer" related pathway on "Ras signaling pathway" and "MAPK signaling pathway". RASF3 is the smallest protein gene in the C-terminal members of the RASSF family. RASSF3 plays a role in tumor inhibition by regulating apoptosis, p53-dependent DNA repair, and cell cycle . Studies by Fukatsu1 et al. have shown that the expression level of RASSF3 is down-regulated in non-small cell lung cancer. The down-regulation of gene expression is closely related to the progressive phenotype of NSCLC, and in vitro studies have also shown that the down-regulation of RASSF3 increases the mobility of lung cancer cells. Kudo et al.  showed that RASSF3 expression induced p53-dependent apoptosis, and its consumption weakened DNA damage-induced apoptosis. The Cytospace software screened out the Hub genes with the top 10 scores, indicating that the genes closely related to the occurrence and development of breast cancer were: HSA-MIRI-23B-3P, OIP5-AS1, MAP4K4, and HSA-MIRI-137. A literature search of the Hub gene revealed that the gene OIP5-AS1 was closely related to the occurrence and development of SCLC. OIP5-AS1, a gene reverse transcription product of OIP 5, is located on human chromosome 15q15.1. It is a newly discovered lncRNA that shows abnormal expression in malignant tumors such as lung cancer, cervical cancer, osteosarcoma, glioma, and melanoma, regulates malignant biological behaviors such as tumor proliferation, migration, and invasion, and is closely related to lymphatic metastasis and patient prognosis . Wang et al.  found that the expression of OIP5-AS1 in lung cancer was increased and was closely related to the tumor size and prognosis of patients. The results showed that OIP5- AS1, as ceRNA, binds to MIRI-378A-3P and inhibits the expression of cyclin-dependent kinase 4/6 (CDK4 /6) downstream of MIRI-378A-3P, thereby promoting the proliferation of tumor cells. In the latest research, Zhang et al.  adopted the qRT-PCR method to detect the expression levels of OIP5-AS1 and miR-511-3p, and adopted MTT and Transwell methods to detect the cell proliferation, migration, and invasion. At the same time, the western blot method was used to detect the protein expression levels of CyclinD1 and MMP-2, and a double luciferase reporting experiment was used to detect the targeting relationship between OIP5-AS1 and miR-511-3p. The results showed that LncRNA OIP5-AS1 inhibited the proliferation, migration, and invasion of lung cancer cells by targeting and regulating the expression of miR-511-3p. Esfandi et al.  studied the expression of OIP5-AS1 in non-small cell lung cancer and the results showed that the expression level of OIP5-AS in tumor tissues was significantly reduced compared with those of non-tumor patients. These studies suggest that RASSF3 and OIP5-AS may be potential tumor-critical target genes for SCLC.