Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway
Abstract Background Lung adenocarcinoma (LUAD), a widespread histopathological subtype of lung cancer, is deemed as a malignant tumor with a peak risk of mortality. Emerged as RNA with a loop structure that depleted protein coding ability, circular RNA (circRNA) has been identified as a regulator in...
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-019-1065-x |
| _version_ | 1818647620785012736 |
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| author | Nan Gao Baoguo Ye |
| author_facet | Nan Gao Baoguo Ye |
| author_sort | Nan Gao |
| collection | DOAJ |
| description | Abstract Background Lung adenocarcinoma (LUAD), a widespread histopathological subtype of lung cancer, is deemed as a malignant tumor with a peak risk of mortality. Emerged as RNA with a loop structure that depleted protein coding ability, circular RNA (circRNA) has been identified as a regulator in cancer progression. Circ-SOX4, identified as a novel circRNA, has not been studied in any cancer yet. Thus, the regulatory function that circ-SOX4 exerts on LUAD development remains obscure. Aim of the study This study aimed to investigate the biological function and molecular mechanism of circ-SOX4 in LUAD. Methods The expression of circ-SOX4 was detected by qRT-PCR. CCK-8, colony formation, transwell and wound healing assays were performed to explore the biological function of circ-SOX4 in LUAD. The interaction between miR-1270 and circ-SOX41 (or PLAGL2) was confirmed by RNA pull down, luciferase reporter and RIP assays. Results Circ-SOX4 was found to be obviously upregulated in LUAD tissues and cells, and knockdown of it inhibited cell proliferation, invasion and migration in LUAD. Furthermore, silenced circ-SOX4 also inhibited LUAD tumor growth. Molecular mechanism assays revealed that circ-SOX4 interacted with miR-1270 in LUAD. Besides, PLAGL2 was confirmed as a downstream gene of miR-1270. Rescue assays validated that miR-1270 suppression or PLAGL2 overexpression countervailed circ-SOX4 depletion-mediated inhibition on cell proliferation, invasion and migration in LUAD. Additionally, it was discovered that circ-SOX4/miR-1270/PLAGL2 axis activated WNT signaling pathway in LUAD. Conclusions Circ-SOX4 boosted the development of LUAD and activate WNT signaling pathway through sponging miR-1270 and modulating PLAGL2, which provided a valuable theoretical basis for exploring underlying therapeutic target in LUAD. |
| first_indexed | 2024-12-17T01:05:26Z |
| format | Article |
| id | doaj.art-56799a74ded9481382ee5cc7afd1555e |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-17T01:05:26Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-56799a74ded9481382ee5cc7afd1555e2022-12-21T22:09:16ZengBMCCancer Cell International1475-28672020-01-0120111210.1186/s12935-019-1065-xCirc-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathwayNan Gao0Baoguo Ye1Department of Thoracic Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Anesthesiology, China-Japan Union Hospital of Jilin UniversityAbstract Background Lung adenocarcinoma (LUAD), a widespread histopathological subtype of lung cancer, is deemed as a malignant tumor with a peak risk of mortality. Emerged as RNA with a loop structure that depleted protein coding ability, circular RNA (circRNA) has been identified as a regulator in cancer progression. Circ-SOX4, identified as a novel circRNA, has not been studied in any cancer yet. Thus, the regulatory function that circ-SOX4 exerts on LUAD development remains obscure. Aim of the study This study aimed to investigate the biological function and molecular mechanism of circ-SOX4 in LUAD. Methods The expression of circ-SOX4 was detected by qRT-PCR. CCK-8, colony formation, transwell and wound healing assays were performed to explore the biological function of circ-SOX4 in LUAD. The interaction between miR-1270 and circ-SOX41 (or PLAGL2) was confirmed by RNA pull down, luciferase reporter and RIP assays. Results Circ-SOX4 was found to be obviously upregulated in LUAD tissues and cells, and knockdown of it inhibited cell proliferation, invasion and migration in LUAD. Furthermore, silenced circ-SOX4 also inhibited LUAD tumor growth. Molecular mechanism assays revealed that circ-SOX4 interacted with miR-1270 in LUAD. Besides, PLAGL2 was confirmed as a downstream gene of miR-1270. Rescue assays validated that miR-1270 suppression or PLAGL2 overexpression countervailed circ-SOX4 depletion-mediated inhibition on cell proliferation, invasion and migration in LUAD. Additionally, it was discovered that circ-SOX4/miR-1270/PLAGL2 axis activated WNT signaling pathway in LUAD. Conclusions Circ-SOX4 boosted the development of LUAD and activate WNT signaling pathway through sponging miR-1270 and modulating PLAGL2, which provided a valuable theoretical basis for exploring underlying therapeutic target in LUAD.https://doi.org/10.1186/s12935-019-1065-xCirc-SOX4miR-1270PLAGL2WNTLUAD |
| spellingShingle | Nan Gao Baoguo Ye Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway Cancer Cell International Circ-SOX4 miR-1270 PLAGL2 WNT LUAD |
| title | Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway |
| title_full | Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway |
| title_fullStr | Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway |
| title_full_unstemmed | Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway |
| title_short | Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway |
| title_sort | circ sox4 drives the tumorigenesis and development of lung adenocarcinoma via sponging mir 1270 and modulating plagl2 to activate wnt signaling pathway |
| topic | Circ-SOX4 miR-1270 PLAGL2 WNT LUAD |
| url | https://doi.org/10.1186/s12935-019-1065-x |
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