Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathway
Abstract Background Till now, no study has focused on the functions of RNASEH1 antisense RNA 1 (RNASEH1‐AS1) in non‐small cell lung cancer (NSCLC). Accordingly, we measured the expression of RNASEH1‐AS1 in NSCLC and characterized its functions in detail. Finally, our research elucidated the mechanis...
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4509 |
| _version_ | 1811271910759071744 |
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| author | Chan Zhang Jian Huang Ke Lou Hui Ouyang |
| author_facet | Chan Zhang Jian Huang Ke Lou Hui Ouyang |
| author_sort | Chan Zhang |
| collection | DOAJ |
| description | Abstract Background Till now, no study has focused on the functions of RNASEH1 antisense RNA 1 (RNASEH1‐AS1) in non‐small cell lung cancer (NSCLC). Accordingly, we measured the expression of RNASEH1‐AS1 in NSCLC and characterized its functions in detail. Finally, our research elucidated the mechanisms that occurred downstream of RNASEH1‐AS1. Methods RNASEH1‐AS1 expression was examined utilizing TCGA database and qRT‐PCR. Functional experiments were conducted to study the tumor‐associated functions of RNASEH1‐AS1. The targeting relationship among RNASEH1‐AS1, microRNA‐516a‐5p (miR‐516a‐5p), and forkhead box K1 (FOXK1) was revealed utilizing RNA immunoprecipitation and luciferase reporter assays. Results Utilizing TCGA database and our own cohort, we found a significantly increased level of RNASEH1‐AS1 in NSCLC. The high level of RNASEH1‐AS1 was markedly related with poor clinical outcomes. Knockdown of RNASEH1‐AS1 expression inhibited NSCLC cell growth, metastatic capacities, and epithelial‐mesenchymal transition and promoted the apoptosis in vitro, whereas RNASEH1‐AS1 overexpression exerted the opposite effects. Additionally, knocking down RNASEH1‐AS1 expression suppressed tumor growth in vivo. RNASEH1‐AS1 was confirmed to act as a miR‐516a‐5p sponge, consequently upregulating FOXK1 expression in NSCLC cells. As revealed by the subsequent rescue experiments, the miR‐516a‐5p/FOXK1 axis served as a downstream effector of RNASEH1‐AS1. In addition, by controlling the miR‐516a‐5p/FOXK1 axis, RNASEH1‐AS1 was capable of activating the Wnt/β‐catenin pathway. Conclusion RNASEH1‐AS1 exacerbated the oncogenicity of NSCLC by affecting the miR‐516a‐5p/FOXK1 axis and consequently promoting the activation of Wnt/β‐catenin pathway. Our newly identified RNASEH1‐AS1/miR‐516a‐5p/FOXK1/Wnt/β‐catenin network may offer an interesting foundation for NSCLC treatment in the clinic. |
| first_indexed | 2024-04-12T22:30:38Z |
| format | Article |
| id | doaj.art-81545d2b63404ae3be380b0c70a686dc |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-12T22:30:38Z |
| publishDate | 2022-04-01 |
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| series | Cancer Medicine |
| spelling | doaj.art-81545d2b63404ae3be380b0c70a686dc2022-12-22T03:13:59ZengWileyCancer Medicine2045-76342022-04-011171589160410.1002/cam4.4509Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathwayChan Zhang0Jian Huang1Ke Lou2Hui Ouyang3Department of Respiratory Medicine The Fourth Hospital of Changsha Changsha Hunan ChinaDepartment of Respiratory Medicine The Fourth Hospital of Changsha Changsha Hunan ChinaDepartment of Respiratory Medicine The Fourth Hospital of Changsha Changsha Hunan ChinaDepartment of Respiratory Medicine The Fourth Hospital of Changsha Changsha Hunan ChinaAbstract Background Till now, no study has focused on the functions of RNASEH1 antisense RNA 1 (RNASEH1‐AS1) in non‐small cell lung cancer (NSCLC). Accordingly, we measured the expression of RNASEH1‐AS1 in NSCLC and characterized its functions in detail. Finally, our research elucidated the mechanisms that occurred downstream of RNASEH1‐AS1. Methods RNASEH1‐AS1 expression was examined utilizing TCGA database and qRT‐PCR. Functional experiments were conducted to study the tumor‐associated functions of RNASEH1‐AS1. The targeting relationship among RNASEH1‐AS1, microRNA‐516a‐5p (miR‐516a‐5p), and forkhead box K1 (FOXK1) was revealed utilizing RNA immunoprecipitation and luciferase reporter assays. Results Utilizing TCGA database and our own cohort, we found a significantly increased level of RNASEH1‐AS1 in NSCLC. The high level of RNASEH1‐AS1 was markedly related with poor clinical outcomes. Knockdown of RNASEH1‐AS1 expression inhibited NSCLC cell growth, metastatic capacities, and epithelial‐mesenchymal transition and promoted the apoptosis in vitro, whereas RNASEH1‐AS1 overexpression exerted the opposite effects. Additionally, knocking down RNASEH1‐AS1 expression suppressed tumor growth in vivo. RNASEH1‐AS1 was confirmed to act as a miR‐516a‐5p sponge, consequently upregulating FOXK1 expression in NSCLC cells. As revealed by the subsequent rescue experiments, the miR‐516a‐5p/FOXK1 axis served as a downstream effector of RNASEH1‐AS1. In addition, by controlling the miR‐516a‐5p/FOXK1 axis, RNASEH1‐AS1 was capable of activating the Wnt/β‐catenin pathway. Conclusion RNASEH1‐AS1 exacerbated the oncogenicity of NSCLC by affecting the miR‐516a‐5p/FOXK1 axis and consequently promoting the activation of Wnt/β‐catenin pathway. Our newly identified RNASEH1‐AS1/miR‐516a‐5p/FOXK1/Wnt/β‐catenin network may offer an interesting foundation for NSCLC treatment in the clinic.https://doi.org/10.1002/cam4.4509ceRNA networkepithelial‐mesenchymal transitionRNASEH1 antisense RNA 1Wnt/β‐catenin pathway |
| spellingShingle | Chan Zhang Jian Huang Ke Lou Hui Ouyang Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathway Cancer Medicine ceRNA network epithelial‐mesenchymal transition RNASEH1 antisense RNA 1 Wnt/β‐catenin pathway |
| title | Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathway |
| title_full | Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathway |
| title_fullStr | Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathway |
| title_full_unstemmed | Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathway |
| title_short | Long noncoding RNASEH1‐AS1 exacerbates the progression of non‐small cell lung cancer by acting as a ceRNA to regulate microRNA‐516a‐5p/FOXK1 and thereby activating the Wnt/β‐catenin signaling pathway |
| title_sort | long noncoding rnaseh1 as1 exacerbates the progression of non small cell lung cancer by acting as a cerna to regulate microrna 516a 5p foxk1 and thereby activating the wnt β catenin signaling pathway |
| topic | ceRNA network epithelial‐mesenchymal transition RNASEH1 antisense RNA 1 Wnt/β‐catenin pathway |
| url | https://doi.org/10.1002/cam4.4509 |
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