Integrative analysis of exosomal microRNA-149-5p in lung adenocarcinoma

Abstract

Exosomes play important roles in the regulation of various processes in the tumor microenvironment. In this study, we explored the mechanisms of exosomal miR-149-5p in the pathogenesis of lung adenocarcinoma. Raw data were downloaded and normalized using the R package. Significantly expressed exosomal miRNAs were subjected to co-expression network analysis. The proliferation and apoptotic abilities of tumor cells were assessed by the proliferation and apoptosis assays. Univariate and multivariate analyses were performed to identify the independent risk factors of exosomal miR-149-5p and AMOTL2. Results showed that exosomal miR-149-5p was enriched in peripheral serum and tumor cells. The upregulation of exosomal miR-149-5p promoted the growth of tumor cells and inhibited apoptosis of tumor cells. Notably, AMOTL2, the target gene of exosomal miR-149-5p, was significantly downregulated in lung adenocarcinoma and may be considered as an independent risk factor of poor survival. In lung adenocarcinoma cells, AMOTL2 downregulation reversed the promoting effect of miR-149-5p on A549 cells growth and the inhibition effect of miR-149-5p on A549 cells apoptosis. Collectively, these results provide specific insights for further mechanistic studies on lung adenocarcinoma.

The Underlying Roles of Exosome-Associated PIGR in Fatty Acid Metabolism and Immune Signaling in Colorectal Cancer

“…As important mediators of intercellular communication, exosomes provide an alternative cargo-handling mechanism to maintain homeostasis and cell survival [29]. Exosomes enhanced or inhibited certain important mediators and changed the tumor microenvironment, thereby altering the occurrence and development of different types of tumors [30][31][32]. Some differentially expressed RNAs and proteins in exosomes have been identified as potential biomarkers linked to CRC initiation and progression.…”

A Review on the Role of miR-149-5p in the Carcinogenesis

“…Moreover, over-expression of miR-149-5p in cancer-derived exosomes could enhance growth of tumor cells and inhibit their apoptosis through suppression of AMOTL2 levels [ 34 ].…”

“…However, another study has shown up-regulation of circPVT1, a miR-149-5p-sequestering circRNA in this type of cancer [ 20 ]. In lung cancer, while most studies have indicated a tumor suppressor role for miR-149-5p ( Table 3 ), assessment of a GEO dataset has shown up-regulation of this miRNA in cancer patients compared with controls [ 34 ].…”

MiR-149-5p: An Important miRNA Regulated by Competing Endogenous RNAs in Diverse Human Cancers

“…The results of ROC curve analysis showed that exosome miR-149-5p was of good value in the diagnosis of LUAD. Exosome miR-149-5p can directly bind to AMOTL2 and mediate tumor cell proliferation and apoptosis, suggesting that exosome miR-149-5p may be a reliable biomarker of TME in LUAD (17).…”

“…Recently, mounting evidences have indicated the pleiotropic functions of miR-149-5p in different human cancers. MiR-149-5p serves as tumor suppressor in several cancers by targeting specific mRNA expression, such as gastric cancer (GC) (13), breast cancer (14), hepatocellular carcinoma (HCC) (15), and colorectal cancer (CRC) (16), whereas in lung adenocarcinoma (LUAD) (17), acute lymphoblastic leukemia (ALL) (18), and acute myeloid leukemia (AML) (19), it acts as oncomiR, promoting tumorigenesis and aggression (20). Intriguingly, miR-149-5p was reported to be regulated by lncRNAs and circRNAs in cancer development, such as LINC00460 in CRC, CircNRIP1 in GC, and hsa_circ_0075341 in cervical cancer (13,16,(21)(22)(23).…”