A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression
nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886′s tumor suppressor role in ESCC. However, this o...
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MDPI AG
2020-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/801 |
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| author | Wonkyun Ronny Im Hyun-Sung Lee Yeon-Su Lee Ju-Seog Lee Hee-Jin Jang Seon-Young Kim Jong-Lyul Park Yeontaek Lee Moon Soo Kim Jong Mog Lee In-Hoo Kim Sung Ho Jeon Yong Sun Lee |
| author_facet | Wonkyun Ronny Im Hyun-Sung Lee Yeon-Su Lee Ju-Seog Lee Hee-Jin Jang Seon-Young Kim Jong-Lyul Park Yeontaek Lee Moon Soo Kim Jong Mog Lee In-Hoo Kim Sung Ho Jeon Yong Sun Lee |
| author_sort | Wonkyun Ronny Im |
| collection | DOAJ |
| description | nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886′s tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study about nc886′s impact on gene expression and cellular phenotypes. Here we have shown that nc886 inhibits AKT, a key protein in a renowned pro-survival pathway in cancer. nc886-silenced cells (nc886<sup>-</sup> cells) have activated AKT and altered expression of cell cycle genes. nc886<sup>-</sup> cells tend to have lower expression of CDKN2A and CDKN2C, both of which are inhibitors for cyclin-dependent kinase (CDK), and higher expression of CDK4 than nc886-expressing cells. As a result, nc886<sup>-</sup> cells are hyperactive in the progression of the G1 to S cell cycle phase, proliferate faster, and are more sensitive to palbociclib, which is a cancer therapeutic drug that targets CDK4/6. Experimentally by nc886 expression and knockdown, we have determined the AKT target genes and cell cycle genes that are controlled by nc886 (nc886-associated gene sets). These gene sets, in combination with pathologic staging and nc886 expression levels, are a vastly superior predictor for the survival of 108 ESCC patients. In summary, our study has elucidated in ESCC how nc886 inhibits cell proliferation to explain its tumor suppressor role and identified gene sets that are of future clinical utility, by predicting patient survival and responsiveness to a therapeutic drug. |
| first_indexed | 2024-03-12T20:01:50Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T20:01:50Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-56585f4f8f7a47b790b378fb3680d8df2023-08-02T02:23:41ZengMDPI AGCells2073-44092020-03-019480110.3390/cells9040801cells9040801A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle ProgressionWonkyun Ronny Im0Hyun-Sung Lee1Yeon-Su Lee2Ju-Seog Lee3Hee-Jin Jang4Seon-Young Kim5Jong-Lyul Park6Yeontaek Lee7Moon Soo Kim8Jong Mog Lee9In-Hoo Kim10Sung Ho Jeon11Yong Sun Lee12Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, KoreaDivision of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USARare Cancer Branch, Research Institute, National Cancer Center, Goyang 10408, KoreaDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADivision of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USAMedical Genomics Research Center, KRIBB, Daejeon 34141, KoreaMedical Genomics Research Center, KRIBB, Daejeon 34141, KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, KoreaCenter for Lung Cancer, National Cancer Center, Goyang 10408, KoreaCenter for Lung Cancer, National Cancer Center, Goyang 10408, KoreaDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, KoreaDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Koreanc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886′s tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study about nc886′s impact on gene expression and cellular phenotypes. Here we have shown that nc886 inhibits AKT, a key protein in a renowned pro-survival pathway in cancer. nc886-silenced cells (nc886<sup>-</sup> cells) have activated AKT and altered expression of cell cycle genes. nc886<sup>-</sup> cells tend to have lower expression of CDKN2A and CDKN2C, both of which are inhibitors for cyclin-dependent kinase (CDK), and higher expression of CDK4 than nc886-expressing cells. As a result, nc886<sup>-</sup> cells are hyperactive in the progression of the G1 to S cell cycle phase, proliferate faster, and are more sensitive to palbociclib, which is a cancer therapeutic drug that targets CDK4/6. Experimentally by nc886 expression and knockdown, we have determined the AKT target genes and cell cycle genes that are controlled by nc886 (nc886-associated gene sets). These gene sets, in combination with pathologic staging and nc886 expression levels, are a vastly superior predictor for the survival of 108 ESCC patients. In summary, our study has elucidated in ESCC how nc886 inhibits cell proliferation to explain its tumor suppressor role and identified gene sets that are of future clinical utility, by predicting patient survival and responsiveness to a therapeutic drug.https://www.mdpi.com/2073-4409/9/4/801nc886esophageal cancercell cycleaktprognosis |
| spellingShingle | Wonkyun Ronny Im Hyun-Sung Lee Yeon-Su Lee Ju-Seog Lee Hee-Jin Jang Seon-Young Kim Jong-Lyul Park Yeontaek Lee Moon Soo Kim Jong Mog Lee In-Hoo Kim Sung Ho Jeon Yong Sun Lee A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression Cells nc886 esophageal cancer cell cycle akt prognosis |
| title | A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression |
| title_full | A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression |
| title_fullStr | A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression |
| title_full_unstemmed | A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression |
| title_short | A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression |
| title_sort | regulatory noncoding rna nc886 suppresses esophageal cancer by inhibiting the akt pathway and cell cycle progression |
| topic | nc886 esophageal cancer cell cycle akt prognosis |
| url | https://www.mdpi.com/2073-4409/9/4/801 |
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