Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis
Abstract Background N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcin...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-021-02368-y |
| _version_ | 1797699147350933504 |
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| author | Peng Xu Kang Hu Ping Zhang Zhi-Gang Sun Nan Zhang |
| author_facet | Peng Xu Kang Hu Ping Zhang Zhi-Gang Sun Nan Zhang |
| author_sort | Peng Xu |
| collection | DOAJ |
| description | Abstract Background N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcinoma (LUSC) remains elusive. Methods The knockdown and overexpression of YTHDF2 in LUSC cells were conducted to detect the biological characteristics of YTHDF2. In vivo assays, the role of YTHDF2 in tumor growth was further uncovered. In vitro assays, YTHDF2 was confirmed to be involved in activating the mTOR/AKT signaling and YTHDF2 overexpression induced the EMT process in LUSC. Clinically, immunohistochemical staining revealed the relationship between YTHDF2 expression levels and the clinicopathological characteristics of lung squamous cell carcinoma patients. Moreover, quantitative PCR (qPCR), western blot, CCK8 assay, transwell assay, and wound-healing assay were used to detect the expression level and function of YTHDF2 under hypoxia exposure in LUSC cells. Results The results showed that hypoxia-mediated YTHDF2 overexpression promotes cell proliferation and invasion by activating the mTOR/AKT axis, and YTHDF2 overexpression induces the EMT process in LUSC. Moreover, YTHDF2 is closely associated with pN (pN– 37.0%, pN + 73.9%; P = 0.002) and pTNM stage (pI 50.0%, PII 43.3%, pIIIa 80.6%; P = 0.007), ultimately resulting in poor survival for LUSC patients. Conclusion In brief, the results highlight high-YTHDF2 expression predicted a worse prognosis of LUSC, while hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT signaling pathway. |
| first_indexed | 2024-03-12T04:03:49Z |
| format | Article |
| id | doaj.art-8ce5df2671bb43b59f0e5906634f80b7 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-12T04:03:49Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-8ce5df2671bb43b59f0e5906634f80b72023-09-03T11:25:42ZengBMCCancer Cell International1475-28672022-01-0122111310.1186/s12935-021-02368-yHypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axisPeng Xu0Kang Hu1Ping Zhang2Zhi-Gang Sun3Nan Zhang4Cheeloo College of Medicine, Shandong UniversitySchool of Clinical Medicine, Weifang Medical UniversityCheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Oncology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract Background N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcinoma (LUSC) remains elusive. Methods The knockdown and overexpression of YTHDF2 in LUSC cells were conducted to detect the biological characteristics of YTHDF2. In vivo assays, the role of YTHDF2 in tumor growth was further uncovered. In vitro assays, YTHDF2 was confirmed to be involved in activating the mTOR/AKT signaling and YTHDF2 overexpression induced the EMT process in LUSC. Clinically, immunohistochemical staining revealed the relationship between YTHDF2 expression levels and the clinicopathological characteristics of lung squamous cell carcinoma patients. Moreover, quantitative PCR (qPCR), western blot, CCK8 assay, transwell assay, and wound-healing assay were used to detect the expression level and function of YTHDF2 under hypoxia exposure in LUSC cells. Results The results showed that hypoxia-mediated YTHDF2 overexpression promotes cell proliferation and invasion by activating the mTOR/AKT axis, and YTHDF2 overexpression induces the EMT process in LUSC. Moreover, YTHDF2 is closely associated with pN (pN– 37.0%, pN + 73.9%; P = 0.002) and pTNM stage (pI 50.0%, PII 43.3%, pIIIa 80.6%; P = 0.007), ultimately resulting in poor survival for LUSC patients. Conclusion In brief, the results highlight high-YTHDF2 expression predicted a worse prognosis of LUSC, while hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT signaling pathway.https://doi.org/10.1186/s12935-021-02368-yYTHDF2HypoxiamTOR/AKTEMTMETTL14LUSC |
| spellingShingle | Peng Xu Kang Hu Ping Zhang Zhi-Gang Sun Nan Zhang Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis Cancer Cell International YTHDF2 Hypoxia mTOR/AKT EMT METTL14 LUSC |
| title | Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis |
| title_full | Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis |
| title_fullStr | Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis |
| title_full_unstemmed | Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis |
| title_short | Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis |
| title_sort | hypoxia mediated ythdf2 overexpression promotes lung squamous cell carcinoma progression by activation of the mtor akt axis |
| topic | YTHDF2 Hypoxia mTOR/AKT EMT METTL14 LUSC |
| url | https://doi.org/10.1186/s12935-021-02368-y |
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