Exosomal miR-1260b derived from non-small cell lung cancer promotes tumor metastasis through the inhibition of HIPK2.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim DH
PROVIDER: S-EPMC8319168 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Lung cancer remains the leading cause of cancer-related death worldwide. Recently, extracellular vesicles such as exosomes have attracted considerable interest both as a source for theranostic biomarkers and an essential participant in lung cancer progression. However, how specific exosomal cargos, such as noncoding RNAs, are selectively packaged into exosomes and promote lung cancer progression remains unclear. In this study, we identified miR-665 as the most elevated exosomal miRNA from both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients. We further demonstrated that lncRNA SCIRT was also increased in cancer cell exosomes and may facilitate the exosomal loading of miR-665 with the help of hnRNPA1. As a consequence, exosomal miR-665 promoted lung cancer cell invasion and migration by targeting Notch downstream transcription factor HEYL. In addition, we found that miR-665 and SCIRT were significantly upregulated in tumor tissue and plasma of patients with lung cancer, and both of them showed increased expression in metastatic disease samples. Our findings suggest that the exosomal transferring of miR-665 and SCIRT is a functional and mechanism-driven pathway that contributes to cancer progression and, thus, may provide novel diagnostic and therapeutic targets for lung cancer.
| S-EPMC8328715 | biostudies-literature
Project description:BackgroundIntercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation.MethodsCancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker.ResultsWe found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641.ConclusionThe findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment. Video Abstract.
| S-EPMC7898766 | biostudies-literature
Project description: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.
| S-EPMC8426367 | biostudies-literature
Project description:BackgroundHigh incidence of metastasis is the main cause of death for small cell lung cancer (SCLC), with its underlying molecular mechanisms remain unclear. Exosomal miRNAs are important regulators in metastatic processes of various tumors, but their specific role in SCLC metastasis is unknown.MethodsSmall RNA sequencing followed by qRT-PCR verification was used to screen the potential exosomal miRNAs that might mediate SCLC metastasis. SCLC-cell-secreted exosomes were labeled followed by incubating with vascular endothelial cells to evaluate exosome-mediated communication between SCLC cells and vascular endothelial cells. In vitro permeability assay and transendothelial migration assay were applied to investigate the function of exosomal miRNA on vascular endothelial cells. In vivo permeability assay and mouse lung colonization assay were used to verify the effects of exosomal miRNA on vascular barriers and SCLC metastasis in vivo. Proteomics technology, dual-luciferase reporter system together with rescue assays were conducted to excavate the downstream pathways of miRNA.ResultsCompared with 57 healthy volunteers and 46 non-small cell lung cancer patients, we identified that the level of exosomal miR-375-3p in 126 SCLC patients was obviously higher and was positively correlated with patient TNM stages. In vitro functional experiments found that SCLC-cell-secreted exosomal miR-375-3p could increase the permeability of vascular endothelial cells and facilitate the transendothelial migration of SCLC cells. In vivo, miR-375-3p-enriched exosomes also destroyed the barrier structure of lung, liver and brain tissues of mice, leaded to an increased blood vessel permeability and finally promoted SCLC metastasis. Mechanistically, SCLC-cell-secreted exosomal miR-375-3p was transferred to vascular endothelial cells. The internalized miR-375-3p broke the tight junction of vascular endothelial cells by directedly binding to the 3'UTR of tight junction protein claudin-1 and negatively regulating its expression. Overexpressing claudin-1 in vascular endothelial cells could rescue the broken vascular barriers induced by miR-375-3p.ConclusionsOur findings underline the crucial roles of exosomal miRNA-375-3p in regulating vascular endothelial barrier integrity and SCLC metastasis. miRNA-375-3p has a great potential to be a novel biomarker monitoring metastasis and guiding clinical therapeutics of SCLC patients.
| S-EPMC8350081 | biostudies-literature
Project description:BACKGROUND:Angiogenesis, a basic requirement for tumor cell survival, is considered to be a malignant characteristic of small cell lung cancer (SCLC) and is closely related to the poor outcomes of SCLC patients. miR-141 has been found to play pro- and antiangiogenic roles in different cancers, but its role in SCLC angiogenesis has never been explored. METHODS:Total RNA was isolated from plasm exosomes and serum of SCLC patients to examine the expression of miR-141 by qRT-PCR. Cell proliferation, invasion, migration, tube formation assay, aortic ring assay and mouse tumor model were used to investigate the effect of exosomal miR-141 in angiogenesis in vitro and in vivo. Dual-luciferase assay was conducted to explore the target gene of miR-141. RESULTS:Circulating miR-141 was upregulated in samples from 122 SCLC patients compared with those from normal volunteers and that the increase in miR-141 was significantly associated with advanced TNM stages, implying the potential oncogenic role of miR-141 in SCLC malignancy. In vitro, miR-141 that was packaged into SCLC cell-secreted exosomes and delivered to human umbilical vein vascular endothelial cells (HUVECs) via exosomes facilitated HUVEC proliferation, invasion, migration and tube formation and promoted microvessel sprouting from mouse aortic rings. Matrigel plug assays demonstrated that SCLC cell-derived exosomal miR-141 induced neoangiogenesis in vivo. Furthermore, mouse subcutaneous tumor nodules that were developed from miR-141-overexpressing SCLC cells had a higher microvessel density (MVD) and grew faster than those developed from negative control cells. KLF12 was found to be the direct target gene of miR-141 and that the proangiogenic effect of miR-141 on HUVECs was abrogated by KLF12 overexpression. CONCLUSIONS:Our results demonstrate the specific function of the exosomal miR-141/KLF12 pathway in SCLC angiogenesis for the first time and provide potential novel targets for antiangiogenic therapies for SCLC patients.
| S-EPMC7504642 | biostudies-literature
Project description:Peritoneal metastasis develops in more than half of patients with gastric cancer but influencing factors are poorly characterized. Exosomes are increasingly recognized as a new mediator in cancer directional metastasis through the transfer of nucleic acids or proteins to neighboring or distant cells. The role of exosomes in peritoneal metastasis and whether it could establish pre-metastatic milieu are largely unknown. Here, we assessed the migration of gastric cancer (GC) cells and identified that PKH26-labeled exosomes from GC cells can be ingested by peritoneal mesothelial cells (MCs). Additionally, miRNA (miR-106a) that highly enriched in GC-derived exosomes (GC-exos) and essential for destroying the mesothelial barrier was demonstrated through the observation of the injury of the MCs including migratory enhancement and imbalance of apoptosis and proliferation. Moreover, either stimulating miR-106a or treatment with GC-exos could inhibit the expression of Smad7, accompanied by the concurrent elevated α-SMA and fibronectin in MCs. Silencing of miR-106a abolished GC-exos-induced gene expression in MCs. The MCs regain the viability, apoptosis reduction and Smad7 expression after rescue experiment conducted in miR-106a-enriched GC-exos. Xenograft model suggested that exosomal miR-106a had a potential to promote tumor growth through targeting Smad7. Collectively, we revealed that the delivery of miR-106a from GC-exos plays a crucial role in gastric cancer peritoneal metastasis.Abbreviations: MiR-106a: microRNA-106a; Smad7: small mothers against decapentaplegic 7; GC: gastric cancer; MCs: mesothelial cells; Exos: exosomes; HG: high-differentiated gastric cancer cells; LG: low-differentiated gastric cancer cells.
| S-EPMC7217357 | biostudies-literature
Project description:BackgroundExosomes have emerged as critical mediators of intercellular communication. Hypoxia is widely recognized as a key regulator of tumor aggressiveness, and significantly affects exosome release by tumor cells. However, the effects of exosomes derived from hypoxic lung adenocarcinoma (LUAD) cells are poorly understood.MethodsSamples of miRNA isolated from hypoxic LUAD cell-derived exosomes (HExo) and normoxic LUAD cell-derived exosomes (NExo) were sequenced to identify miRNAs that might mediate tumor progression. Exosomal miRNA was co-cultured with LUAD cells to assess its biological effects on cell migration and metastasis both in vitro and in vivo. The cellular target of exosomal miRNA was confirmed by dual-luciferase assays. Western blot studies showed that exosomal miRNA regulated the related pathway. The availability of circulating exosomal miRNA derived from plasma was also evaluated.ResultsWe found that HExo could significantly enhance the migration and invasion of normoxic LUAD cells. MiRNA sequencing results suggested that miR-31-5p was largely internalized within HExo and could be taken up by normoxic LUAD cells. Exosomal miR-31-5p was found to directly target Special AT-Rich Sequence-Binding Protein 2 (SATB2)-revered epithelial mesenchymal transition and significantly increase activation of MEK/ERK signaling, thereby contributing to tumor progression both in vitro and in vivo. Furthermore, higher levels of circulating exosomal miR-31-5p were detected in LUAD patients, especially in patients with metastatic disease.ConclusionsOur findings demonstrate that exosomal miR-31-5p exerts a crucial role in LUAD progression, and could serve as a diagnostic biomarker for LUAD.
| S-EPMC8167983 | biostudies-literature
Project description:Studies have shown that cancer-associated fibroblasts (CAFs) play an irreplaceable role in the occurrence and development of tumors. Therefore, exploring the action and mechanism of CAFs on tumor cells is particularly important. In this study, we compared the effects of CAFs-derived exosomes and normal fibroblasts (NFs)-derived exosomes on breast cancer cells migration and invasion. The results showed that exosomes from both CAFs and NFs could enter into breast cancer cells and CAFs-derived exosomes had a more enhancing effect on breast cancer cells migration and invasion than NFs-derived exosomes. Furthermore, microRNA (miR)-18b was upregulated in CAFs-derived exosomes, and CAFs-derived exosomes miR-18b can promote breast cancer cell migration and metastasis by specifically binding to the 3'UTR of Transcription Elongation Factor A Like 7 (TCEAL7). The miR-18b-TCEAL7 pathway promotes nuclear Snail ectopic activation by activating nuclear factor-kappa B (NF-κB), thereby inducing epithelial-mesenchymal transition (EMT) and promoting cell invasion and metastasis. Moreover, CAFs-derived exosomes miR-18b could promote mouse xenograft model tumor metastasis. Overall, our findings suggest that CAFs-derived exosomes miR-18b promote nuclear Snail ectopic by targeting TCEAL7 to activate the NF-κB pathway, thereby inducing EMT, invasion, and metastasis of breast cancer. Targeting CAFs-derived exosome miR-18b may be a potential treatment option to overcome breast cancer progression.
| S-EPMC8636636 | biostudies-literature
Project description:Cancer-derived exosomal miRNAs are implicated in tumorigenesis and development of lung adenocarcinoma (LUAD). The objective of this study is to unravel the biological function of exosomal miR-197-3p in LUAD metastasis. qRT-PCR showed that elevated miR-197-3p in LUAD tissues was positively correlated with LUAD metastasis. CCK-8, tube formation, transwell and wound healing assays revealed that exosomal miR-197-3p from LUAD cells promoted the proliferation, angiogenesis and migration of HUVECs in vitro. LUAD cells-derived exosomal miR-197-3p also facilitated tumor growth and angiogenesis in LUAD cells-derived tumor xenograft model. TIMP2 and TIMP3 were identified as target genes of miR-197-3p in HUVECs by bioinformatics analysis and luciferase reporter assay. Functional studies illustrated that exosomal miR-197-3p promoted angiogenesis and migration via targeting TIMP2 and TIMP3 in HUVECs. In vivo data further supported that exosomal miR-197-3p promoted lung metastasis via TIMP2/3-mediated angiogenesis. In conclusion, LUAD cells-derived exosomal miR-197-3p conferred angiogenesis via targeting TIMP2/3 in LUAD metastasis.
| S-EPMC9734149 | biostudies-literature
Project description:BackgroundNon-small cell lung cancer is a heterogeneous disease driven by extensive molecular alterations. Exosomes are small vesicles with diameters ranging from 30 to 150 nm released by various cell types and are important mediators of information transmission in tumor cells. Exosomes contain proteins, lipids, and various types of nucleic acids, including miRNAs and even DNA and RNA. MFI2 Antisense RNA 1 (MFI2-AS1) is a long noncoding RNA known to promote cell proliferation, metastasis and invasion in a variety of malignancies.MethodsThe relative expression of MFI2-AS1 in NSCLC tissues was examined using RNA fluorescence in situ hybridization (FISH) staining. Transwell migration and wound healing assays were used to analyze cell migration and invasion abilities. Tube formation is used to assess angiogenic capacity. CCK8 was used to assess cell proliferation ability. RNA immunoprecipitation (RIP) experiments confirmed that MFI2-AS1 acts as a competing endogenous RNA (ceRNA) for miR-107. Dual-luciferase reporter assays were used to identify potential binding between MFI2-miRNA and target mRNA. In vivo experiments were performed by injecting exosomes into subcutaneous tumors to establish animal models.ResultExosomal MFI2-AS1 increases NFAT5 expression by sponging miR-107, which in turn activates the PI3K/AKT pathway. We found that the MFI2-AS1/miR-107/NFAT5 axis plays an important role in exosome-mediated NSCLC progression, is involved in pre-metastatic niche formation, and can be used as a blood-based biomarker for NSCLC metastasis.ConclusionWe demonstrate that MFI2-AS1 is upregulated in exosomes secreted by metastatic NSCLC cells and can be transferred to HUVECs, promoting angiogenesis and migration.
| S-EPMC10024841 | biostudies-literature