Dataset Information

MicroRNA-101 inhibits invasion and angiogenesis through targeting ITGA3 and its systemic delivery inhibits lung metastasis in nasopharyngeal carcinoma.

ABSTRACT: Clinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC), and the treatment outcome of metastatic NPC remains disappointing, so there is a pressing need to identify novel therapeutic strategies. In accordance with our previous microarray data, we found that miR-101 was downregulated in NPC clinical specimens and cell lines. Ectopic expression of miR-101 significantly suppressed NPC cell migration, invasion and angiogenesis in vitro and inhibited angiogenesis and metastasis in vivo using the chicken chorioallantoic membrane model. Furthermore, ITGA3 was identified and validated as a novel target of miR-101, and the restoration of ITGA3 expression potently rescued the suppressive effects of miR-101. In addition, NPC patients with high ITGA3 expression had poorer overall survival and distant metastasis-free survival than patients with low ITGA3 expression, and ITGA3 overexpression was an independent poor prognostic factor in NPC. More importantly, we demonstrated that the systemic delivery of lentivirus-mediated miR-101 abrogated the lung metastatic colonization formation of NPC cells without obvious toxicity. Our study elucidates the molecular mechanisms of miR-101/ITGA3 pathway in regulating NPC metastasis and angiogenesis, and the systemic delivery of miR-101 provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for NPC patients.

SUBMITTER: Tang XR

PROVIDER: S-EPMC5386386 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-101 inhibits invasion and angiogenesis through targeting ITGA3 and its systemic delivery inhibits lung metastasis in nasopharyngeal carcinoma.

Tang Xin-Ran XR Wen Xin X He Qing-Mei QM Li Ying-Qin YQ Ren Xian-Yue XY Yang Xiao-Jing XJ Zhang Jian J Wang Ya-Qin YQ Ma Jun J Liu Na N

Cell death & disease 20170119 1

Clinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC), and the treatment outcome of metastatic NPC remains disappointing, so there is a pressing need to identify novel therapeutic strategies. In accordance with our previous microarray data, we found that miR-101 was downregulated in NPC clinical specimens and cell lines. Ectopic expression of miR-101 significantly suppressed NPC cell migration, invasion and angiogenesis in vitro and inhibi ...[more]

PMID: 28102841

Similar Datasets

Project description:Rationale: Extracellular vesicles (EVs) have emerged as novel mediators of cell-to-cell communication that are capable of the stable transfer of therapeutic microRNAs (miRNAs), and thus, EVs hold immense promise as a miRNA delivery system for cancer therapy. Additionally, as miRNA-containing EVs are secreted into circulation, miRNAs contained within plasma EVs may represent ideal biomarkers for diseases. The objective of this study was to characterize a potential tumor suppressor miRNA, miR-101, and explore the potential of miR-101 delivery via EVs for in vivo therapy of metastatic osteosarcoma as well as the potential value of plasma EV-packaged miR-101 (EV-miR-101) level for predicting osteosarcoma metastasis. Methods: The relationship of miR-101 expression and osteosarcoma progression was investigated in osteosarcoma specimens by in situ hybridization (ISH), and the potential inhibitory effect of miR-101 was further investigated using in vivo models. Using prediction software analysis, the mechanism of action of miR-101 in osteosarcoma was explored using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting and dual-luciferase assay. Adipose tissue-derived mesenchymal stromal cells (AD-MSCs) were transduced with lentiviral particles to obtain miR-101-enriched EVs. A Transwell assay and lung metastasis models of osteosarcoma were used to observe the effect of miR-101-enriched EVs on osteosarcoma invasiveness and metastasis. Detection of plasma EV-miR-101 levels was carried out in osteosarcoma patients and healthy controls by qRT-PCR. Results: miR-101 expression was markedly lower in metastatic osteosarcoma specimens compared to non-metastatic specimens. Significantly fewer metastatic lung nodules were formed by Saos-2 cells overexpressing miR-101 and SOSP-9607 cells overexpressing miR-101 injected into mice. With increased miR-101 expression, B cell lymphoma 6 (BCL6) mRNA and protein expression levels were reduced, and miR-101 was found to exert its effects by directly targeting BCL6. AD-MSCs were successfully engineered to secrete miR-101-enriched EVs. Once taken up by osteosarcoma cells, these EVs showed suppressive effects on cell invasion and migration in vitro, and systemic administration of these EVs effectively suppressed metastasis in vivo with no significant side effects. Finally, the EV-miR-101 level was lower in osteosarcoma patients than in healthy controls and even lower in osteosarcoma patients with metastasis than in those without metastasis. Conclusion: Our data support the function of miR-101 as a tumor suppressor in osteosarcoma via downregulation of BCL6. AD-MSC derived miR-101-enriched EVs represent a potential innovative therapy for metastatic osteosarcoma. EV-miR-101 also represents a promising circulating biomarker of osteosarcoma metastasis.

Project description:As a member of the integrin family, integrin α3β1 (ITGA3) has been linked to intercellular communication and serves an important role in the signaling among cells and the extracellular matrix. MicroRNA (miR)‑199a‑5p has been demonstrated to be related to the pathogenesis and progression of multiple malignant diseases. However, the biological functions of miR‑199a‑5p and ITGA3 in colorectal cancer (CRC) have rarely been reported. The aim of the present study was to explore the roles of miR‑199a‑5p and ITGA3 in CRC. Immunohistochemistry staining and western blotting were applied to detect the protein expression of ITGA3 in CRC tissues and cells. Reverse transcription‑quantitative PCR was performed to investigate the expression of miR‑199a‑5p and ITGA3 mRNA. HCT‑116 cells were transfected with miR‑199a‑5p mimics, mimics control, short hairpin RNA targeting ITGA3, or pcDNA‑ITGA3 for the functional experiments. Dual luciferase reporter assay was applied to confirm whether miR‑199a‑5p targeted the 3' untranslated region (3'UTR) of ITGA3. The MTT, Transwell and wound healing assays were used to evaluate the proliferation, invasion and migration of CRC cells. Immunofluorescence assay was used to monitor the epithelial‑mesenchymal transition (EMT) biomarker expression. The results demonstrated downregulation of miR‑199a‑5p and upregulation of ITGA3 in CRC tissues and cell lines. miR‑199a‑5p mimics and knockdown of ITGA3 suppressed the proliferation, invasion and migration of CRC cells. Bioinformatics analysis and luciferase reporter assay indicated that miR‑199a‑5p targeted the 3'UTR of the ITGA3 transcript, and overexpression of ITGA3 reversed the tumor‑suppressive effects of miR‑199a‑5p elevation. In addition, the immunofluorescence assay suggested that miR‑199a‑5p mimics suppressed the EMT of CRC cells, whereas the overexpression of ITGA3 restored this effect. In conclusion, miR‑199a‑5p may act as a tumor suppressor by targeting and negatively regulating ITGA3 in CRC.

Dataset Information

MicroRNA-101 inhibits invasion and angiogenesis through targeting ITGA3 and its systemic delivery inhibits lung metastasis in nasopharyngeal carcinoma.

Publications

MicroRNA-101 inhibits invasion and angiogenesis through targeting ITGA3 and its systemic delivery inhibits lung metastasis in nasopharyngeal carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets