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Metastasis is the main cause of death in patients with advanced lung cancer. The exosomes released by cancer cells create tumor microenvironment, and then accelerate tumor metastasis. Cancer-derived exosomes are considered to be the main driving force for metastasis niche formation at foreign sites, but the mechanism in Non-small cell lung carcinoma (NSCLC) is unclear. In metastatic NSCLC patients, the expression level of miR-3157-3p in circulating exosomes was significantly higher than that of non-metastatic NSCLC patients. Here, we found that miR-3157-3p can be transferred from NSCLC cells to vascular endothelial cells through exosomes. Our work indicates that exosome miR-3157-3p is involved in the formation of pre-metastatic niche formation before tumor metastasis and may be used as a blood-based biomarker for NSCLC metastasis. Exosome miR-3157-3p has regulated the expression of VEGF/MMP2/MMP9 and occludin in endothelial cells by targeting TIMP/KLF2, thereby promoted angiogenesis and increased vascular permeability. In addition, exosome miR-3157-3p promoted the metastasis of NSCLC in vivo., (© 2021. The Author(s).)

In this study, we explored expression and functions of circular RNA LPAR3 (circLPAR3) in esophageal squamous cell carcinoma (ESCC). The differential expression of circular RNAs (circRNAs) in 10 ESCC and corresponding paracarcinoma tissues was analyzed through circRNA microarray, then the candidate circRNAs were detected and verified through quantitative RT-PCR, and a novel circRNA was screened, which was circLPAR3. Circular RNA LPAR3 showed apparently high expression in ESCC tissues and cells, which was closely correlated with the clinical stage and lymph node metastasis of ESCC patients. Circular RNA LPAR3 was mainly located in the cytoplasm of ESCC cells, which was more stable than the baseline gene. Circular RNA LPAR3 upregulated MET gene expression through sponge adsorption of microRNA (miR)-198, activated the RAS/MAPK and the PI3K/Akt pathways, and promoted ESCC cell migration, invasion, and metastasis in vivo and in vitro. However, it had no effect on ESCC cell proliferation. Circular RNA LPAR3 can regulate the miR-198-MET signal axis to promote the migration, invasion, and metastasis of esophageal cancer cells, which can thereby serve as a potential diagnostic and therapeutic target of esophageal cancer., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Circle RNAs (circRNAs) are the novel noncoding RNAs with the covalent closed-loop structure, which play a crucial role in a variety of pathological processes, including cancer. Nevertheless, the expression profiles and functions of circRNAs in esophageal squamous cell cancer (ESCC) remain largely unknown. In this paper, 10 pairs of ESCC tissues were utilized to screen the circRNA expression profiles by means of microarray assay; further, a novel circular RNA named hsa_circ_0006168 was investigated. Meanwhile, the expression of hsa_circ_0006168 was measured in 52 ESCC tissues and in cell lines. Our results suggested that, hsa_circ_0006168 was remarkably increased not only in ESCC tissues but also in cell lines compared with those in normal cases. Besides, high hsa_circ_0006168 expression was positively connected with lymph node metastasis and TNM stage of ESCC patients. In vitro, the proliferation, invasion and migration capacities of ESCC cells were suppressed through down-regulating hsa_circ_0006168 expression. Besides, RNase R digestion assay confirmed that hsa_circ_0006168 was more stable than its linear CNOT6L mRNA form. Moreover, nuclear and cytoplasmic fraction assay indicated that hsa_circ_0006168 was mainly distributed in the cytoplasm of Kyse450 and TE13 cells. Mechanically, it was discovered in this study that hsa_circ_0006168 might regulate the expression of Mammalian Target of Rapamycin (mTOR) by sponging microRNA-100 (miR-100). Taken together, hsa_circ_0006168 can promote ESCC proliferation, migration and invasion through the competing endogenous RNA (ceRNA) mechanism, which has been first confirmed in our results. In ESCC, hsa_circ_0006168 can serve as a potential diagnostic biomarker and therapeutic target., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

MicroRNA-1204 (miR-1204), a member of the PVT1 region, may improve B cell differentiation and metastasis in breast cancer. However, the role of miR-1204 in non-small-cell lung cancer (NSCLC) and its mechanism remain unclear. The GEO public database was first employed to find differentially expressed genes. The expression level of miR-1204 in patient tissues and NSCLC cell lines was determined using qRT-PCR. Cell proliferation assays were performed to investigate the impact of miR-1204 on cell growth. Bioinformatics analysis and dual-luciferase reporter assays were conducted to find potential target genes. Finally, we performed in vivo experiments to identify the effect of miR-1204 on tumor formation in nude mice. It was first found that miR-1204 was overexpressed in NSCLC tissues and cells. miR-1204 increased the proliferation of NSCLC cells and reduced cell cycle arrest in vitro. PITX1 (paired like homeodomain 1) was found as a potential target gene. In addition, PITX1 was also found to be low in expression in NSCLC tissues and cells. To show that PITX1 reversed the function of miR-1204 in promoting proliferation, confirmatory experiments were performed. Moreover, high miR-1204 and low PITX1 expression was highly correlated with tumor size, lymph node metastasis, and the TNM stage in patients diagnosed with NSCLC. Our results suggested that upregulated miR-1204 in NSCLC is associated with NSCLC progression and promotes NSCLC cell proliferation by downregulating PITX1. miR-1204 may act as a poor prognostic factor and a potential therapeutic target for NSCLC., (© 2018 International Federation for Cell Biology.)

Objectives: Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR-1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR-1258 in non-small-cell lung cancer remains unclear., Methods: The differential expression of miR-1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT-PCR and ISH. Flow cytometry and CCK-8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR-1258. Potential targets of miR-1258 were verified by dual luciferase reporter assay, qRT-PCR, IHC and Western blotting., Results: In vitro and in vivo gain- and loss-of-function assays suggested that miR-1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR-1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR-1258. In contrast, miR-1258 inhibitor significantly reversed si-GRB2-induced GRB2 down-regulation. Mechanistically, overexpression of miR-1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway., Conclusions: Our results indicate that miR-1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients., (© 2018 John Wiley & Sons Ltd.)