LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma
Abstract Background Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Methods The exp...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-020-01652-7 |
| _version_ | 1818589559093460992 |
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| author | Rong-Hang Hu Zi-Teng Zhang Hai-Xiang Wei Lu Ning Jiang-Shan Ai Wen-Hui Li Heng Zhang Shao-Qiang Wang |
| author_facet | Rong-Hang Hu Zi-Teng Zhang Hai-Xiang Wei Lu Ning Jiang-Shan Ai Wen-Hui Li Heng Zhang Shao-Qiang Wang |
| author_sort | Rong-Hang Hu |
| collection | DOAJ |
| description | Abstract Background Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Methods The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. Results ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. Conclusions ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD. |
| first_indexed | 2024-12-16T09:42:34Z |
| format | Article |
| id | doaj.art-91205aa941be48ab891e5cf92cfb9996 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-16T09:42:34Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-91205aa941be48ab891e5cf92cfb99962022-12-21T22:36:13ZengBMCCancer Cell International1475-28672020-12-0120111510.1186/s12935-020-01652-7LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinomaRong-Hang Hu0Zi-Teng Zhang1Hai-Xiang Wei2Lu Ning3Jiang-Shan Ai4Wen-Hui Li5Heng Zhang6Shao-Qiang Wang7Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical UniversityDepartment of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical UniversityDepartment of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical UniversityDepartment of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical UniversityMedical College of Qingdao UniversityDepartment of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical UniversityDepartment of Thoracic Surgery, Xiangya Hospital, Central South UniversityDepartment of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical UniversityAbstract Background Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Methods The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. Results ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. Conclusions ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.https://doi.org/10.1186/s12935-020-01652-7ST7-AS1Lung adenocarcinomaEpithelial-mesenchymal transitionmiR-181b-5pKPNA4 |
| spellingShingle | Rong-Hang Hu Zi-Teng Zhang Hai-Xiang Wei Lu Ning Jiang-Shan Ai Wen-Hui Li Heng Zhang Shao-Qiang Wang LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma Cancer Cell International ST7-AS1 Lung adenocarcinoma Epithelial-mesenchymal transition miR-181b-5p KPNA4 |
| title | LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma |
| title_full | LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma |
| title_fullStr | LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma |
| title_full_unstemmed | LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma |
| title_short | LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma |
| title_sort | lncrna st7 as1 by regulating mir 181b 5p kpna4 axis promotes the malignancy of lung adenocarcinoma |
| topic | ST7-AS1 Lung adenocarcinoma Epithelial-mesenchymal transition miR-181b-5p KPNA4 |
| url | https://doi.org/10.1186/s12935-020-01652-7 |
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