MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK Signalings
Glioma is the most malignant brain tumors in the world, the function and molecular mechanism of microRNA-199a (miR-199a) in glioma is not fully understood. Our research aims to investigate miR-199a/K-RAS axis in regulation of glioma tumor growth and chemoresistance. The function of miR-199a in gliom...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01071/full |
| _version_ | 1818068110693892096 |
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| author | Wei Li Lin Wang Xiang-Bo Ji Li-Hong Wang Xin Ge Wei-Tao Liu Ling Chen Zhong Zheng Zhu-Mei Shi Ling-Zhi Liu Marie C. Lin Jie-Yu Chen Bing-Hua Jiang Bing-Hua Jiang Bing-Hua Jiang |
| author_facet | Wei Li Lin Wang Xiang-Bo Ji Li-Hong Wang Xin Ge Wei-Tao Liu Ling Chen Zhong Zheng Zhu-Mei Shi Ling-Zhi Liu Marie C. Lin Jie-Yu Chen Bing-Hua Jiang Bing-Hua Jiang Bing-Hua Jiang |
| author_sort | Wei Li |
| collection | DOAJ |
| description | Glioma is the most malignant brain tumors in the world, the function and molecular mechanism of microRNA-199a (miR-199a) in glioma is not fully understood. Our research aims to investigate miR-199a/K-RAS axis in regulation of glioma tumor growth and chemoresistance. The function of miR-199a in glioma was investigated through in vitro and in vivo assays. We found that miR-199a in tumor tissues of glioma patients was significantly downregulated in this study. Kinase suppressor of ras 1 (K-RAS), was indicated as a direct target of miR-199a, as well as expression levels of K-RAS were inversely correlated with expression levels of miR-199a in human glioma specimens. Forced expression of miR-199a suppressed AKT and ERK activation, decreased HIF-1α and VEGF expression, inhibited cell proliferation and cell migration, forced expression of K-RAS restored the inhibitory effect of miR-199a on cell proliferation and cell migration. Moreover, miR-199a renders tumor cells more sensitive to temozolomide (TMZ) via targeting K-RAS. In vivo experiment validated that miR-199a functioned as a tumor suppressor, inhibited tumor growth by targeting K-RAS and suppressed activation of AKT, ERK and HIF-1α expression. Taken together, these findings indicated that miR-199a inhibits tumor growth and chemoresistance by regulating K-RAS, and the miR-199a/K-RAS axis is a potential therapeutic target for clinical intervention in glioma. |
| first_indexed | 2024-12-10T15:34:22Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T15:34:22Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6ef1b6bf399d473d8940f664259a59782022-12-22T01:43:17ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-10-01910.3389/fonc.2019.01071483863MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK SignalingsWei Li0Lin Wang1Xiang-Bo Ji2Li-Hong Wang3Xin Ge4Wei-Tao Liu5Ling Chen6Zhong Zheng7Zhu-Mei Shi8Ling-Zhi Liu9Marie C. Lin10Jie-Yu Chen11Bing-Hua Jiang12Bing-Hua Jiang13Bing-Hua Jiang14Department of Pathology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaInstitute of Medical and Pharmaceutical Sciences, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaInstitute of Medical and Pharmaceutical Sciences, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaInstitute of Medical and Pharmaceutical Sciences, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathology, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathology, Nanjing Medical University, Nanjing, ChinaDepartment of Pathology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDepartment of Pathology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathology, Nanjing Medical University, Nanjing, ChinaDepartment of Pathology, Carver College of Medicine, The University of Iowa, Iowa, IA, United StatesInstitute of Medical and Pharmaceutical Sciences, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Pathology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaInstitute of Medical and Pharmaceutical Sciences, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathology, Nanjing Medical University, Nanjing, ChinaDepartment of Pathology, Carver College of Medicine, The University of Iowa, Iowa, IA, United StatesGlioma is the most malignant brain tumors in the world, the function and molecular mechanism of microRNA-199a (miR-199a) in glioma is not fully understood. Our research aims to investigate miR-199a/K-RAS axis in regulation of glioma tumor growth and chemoresistance. The function of miR-199a in glioma was investigated through in vitro and in vivo assays. We found that miR-199a in tumor tissues of glioma patients was significantly downregulated in this study. Kinase suppressor of ras 1 (K-RAS), was indicated as a direct target of miR-199a, as well as expression levels of K-RAS were inversely correlated with expression levels of miR-199a in human glioma specimens. Forced expression of miR-199a suppressed AKT and ERK activation, decreased HIF-1α and VEGF expression, inhibited cell proliferation and cell migration, forced expression of K-RAS restored the inhibitory effect of miR-199a on cell proliferation and cell migration. Moreover, miR-199a renders tumor cells more sensitive to temozolomide (TMZ) via targeting K-RAS. In vivo experiment validated that miR-199a functioned as a tumor suppressor, inhibited tumor growth by targeting K-RAS and suppressed activation of AKT, ERK and HIF-1α expression. Taken together, these findings indicated that miR-199a inhibits tumor growth and chemoresistance by regulating K-RAS, and the miR-199a/K-RAS axis is a potential therapeutic target for clinical intervention in glioma.https://www.frontiersin.org/article/10.3389/fonc.2019.01071/fullmiR-199agliomaK-RASchemoresistancetumorigenesis |
| spellingShingle | Wei Li Lin Wang Xiang-Bo Ji Li-Hong Wang Xin Ge Wei-Tao Liu Ling Chen Zhong Zheng Zhu-Mei Shi Ling-Zhi Liu Marie C. Lin Jie-Yu Chen Bing-Hua Jiang Bing-Hua Jiang Bing-Hua Jiang MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK Signalings Frontiers in Oncology miR-199a glioma K-RAS chemoresistance tumorigenesis |
| title | MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK Signalings |
| title_full | MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK Signalings |
| title_fullStr | MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK Signalings |
| title_full_unstemmed | MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK Signalings |
| title_short | MiR-199a Inhibits Tumor Growth and Attenuates Chemoresistance by Targeting K-RAS via AKT and ERK Signalings |
| title_sort | mir 199a inhibits tumor growth and attenuates chemoresistance by targeting k ras via akt and erk signalings |
| topic | miR-199a glioma K-RAS chemoresistance tumorigenesis |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01071/full |
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