Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain Barrier
Brain metastasis is a severe complication that affects the survival of lung cancer patients. However, the mechanism of brain metastasis in lung cancer remains unclear. In this study, we constructed an in vitro BBB model and found that cells from the high-metastatic nonsmall cell lung cancer (NSCLC)...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.825899/full |
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| author | Sumin Geng Sumin Geng Shaohua Tu Shaohua Tu Zhenwei Bai Zhenwei Bai Yixiong Geng |
| author_facet | Sumin Geng Sumin Geng Shaohua Tu Shaohua Tu Zhenwei Bai Zhenwei Bai Yixiong Geng |
| author_sort | Sumin Geng |
| collection | DOAJ |
| description | Brain metastasis is a severe complication that affects the survival of lung cancer patients. However, the mechanism of brain metastasis in lung cancer remains unclear. In this study, we constructed an in vitro BBB model and found that cells from the high-metastatic nonsmall cell lung cancer (NSCLC) cell line H1299 showed a higher capacity to pass through the blood–brain barrier (BBB), as verified by Transwell assays, than cells from the low-metastatic NSCLC cell line A549. Brain microvascular endothelial cells (BMECs) could internalize H1299-derived exosomes, which remarkably promoted A549 cells across the BBB. The BBB-associated exosomal long noncoding RNA (lncRNA) was selected from the RNA-Seq dataset (GSE126548) and verified by real-time PCR and Transwell assays. LncRNA LINC01356 was significantly upregulated in H1299 cells and exosomes derived from these cells compared to that of A549 cells. Moreover, LINC01356 was also upregulated in serum exosomes of patients with NSCLC with brain metastasis compared with those without metastasis. In addition, BMECs treated with LINC01356-deprived exosomes expressed higher junction proteins than those treated with the control exosomes, and silencing LINC01356 in exosomes derived from H1299 cells could inhibit A549 cells from crossing the BBB. These data might indicate that the exosomal lncRNA LINC01356 derived from brain metastatic NSCLC cells plays a key role in remodeling the BBB system, thereby participating in brain metastasis in lung cancer. |
| first_indexed | 2024-12-12T22:24:09Z |
| format | Article |
| id | doaj.art-71095e7ccc0d4afc81de04047e526670 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T22:24:09Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-71095e7ccc0d4afc81de04047e5266702022-12-22T00:09:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.825899825899Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain BarrierSumin Geng0Sumin Geng1Shaohua Tu2Shaohua Tu3Zhenwei Bai4Zhenwei Bai5Yixiong Geng6Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaSchool of Basic Medical Sciences, Capital Medical University, Beijing, ChinaBrain metastasis is a severe complication that affects the survival of lung cancer patients. However, the mechanism of brain metastasis in lung cancer remains unclear. In this study, we constructed an in vitro BBB model and found that cells from the high-metastatic nonsmall cell lung cancer (NSCLC) cell line H1299 showed a higher capacity to pass through the blood–brain barrier (BBB), as verified by Transwell assays, than cells from the low-metastatic NSCLC cell line A549. Brain microvascular endothelial cells (BMECs) could internalize H1299-derived exosomes, which remarkably promoted A549 cells across the BBB. The BBB-associated exosomal long noncoding RNA (lncRNA) was selected from the RNA-Seq dataset (GSE126548) and verified by real-time PCR and Transwell assays. LncRNA LINC01356 was significantly upregulated in H1299 cells and exosomes derived from these cells compared to that of A549 cells. Moreover, LINC01356 was also upregulated in serum exosomes of patients with NSCLC with brain metastasis compared with those without metastasis. In addition, BMECs treated with LINC01356-deprived exosomes expressed higher junction proteins than those treated with the control exosomes, and silencing LINC01356 in exosomes derived from H1299 cells could inhibit A549 cells from crossing the BBB. These data might indicate that the exosomal lncRNA LINC01356 derived from brain metastatic NSCLC cells plays a key role in remodeling the BBB system, thereby participating in brain metastasis in lung cancer.https://www.frontiersin.org/articles/10.3389/fonc.2022.825899/fulllung cancerlncRNA LINC01356exosomeBBBbrain metastasis |
| spellingShingle | Sumin Geng Sumin Geng Shaohua Tu Shaohua Tu Zhenwei Bai Zhenwei Bai Yixiong Geng Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain Barrier Frontiers in Oncology lung cancer lncRNA LINC01356 exosome BBB brain metastasis |
| title | Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain Barrier |
| title_full | Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain Barrier |
| title_fullStr | Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain Barrier |
| title_full_unstemmed | Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain Barrier |
| title_short | Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood–Brain Barrier |
| title_sort | exosomal lncrna linc01356 derived from brain metastatic nonsmall cell lung cancer cells remodels the blood brain barrier |
| topic | lung cancer lncRNA LINC01356 exosome BBB brain metastasis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.825899/full |
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