Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer
The Krüppel-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in several solid tumors, but its role in PTC remains unclear. We investigated the expression of KLF5 protein in a large cohort of PTC patient samples and explored its functional role and mechanism in PTC cell...
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/2/185 |
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| author | Poyil Pratheeshkumar Abdul K. Siraj Sasidharan Padmaja Divya Sandeep Kumar Parvathareddy Sarah Siraj Roxanne Diaz Rafia Begum Saif S. Al-Sobhi Fouad Al-Dayel Khawla S. Al-Kuraya |
| author_facet | Poyil Pratheeshkumar Abdul K. Siraj Sasidharan Padmaja Divya Sandeep Kumar Parvathareddy Sarah Siraj Roxanne Diaz Rafia Begum Saif S. Al-Sobhi Fouad Al-Dayel Khawla S. Al-Kuraya |
| author_sort | Poyil Pratheeshkumar |
| collection | DOAJ |
| description | The Krüppel-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in several solid tumors, but its role in PTC remains unclear. We investigated the expression of KLF5 protein in a large cohort of PTC patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. KLF5 overexpression was observed in 65.1% of all PTC cases and it was significantly associated with aggressive clinico-pathological parameters and poor outcome. Given the significant association between KLF5 and HIF-1α overexpression in PTC patients, we investigated the functional correlation between KLF5 and HIF-1α in PTC cells. Indeed, the analysis revealed the co-immunoprecipitation of KLF5 with HIF-1α in PTC cells. We also identified KLF5-binding sites in the HIF-1α promoter that specifically bound to KLF5 protein. Mechanistically, KLF5 promoted PTC cell growth, invasion, migration, and angiogenesis, while KLF5 downregulation via specific inhibitor or siRNA reverses its action in vitro. Importantly, the silencing of KLF5 decreases the self-renewal ability of spheroids generated from PTC cells. In addition, the depletion of KLF5 reduces PTC xenograft growth in vivo. These findings suggest KLF5 can be a possible new molecular therapeutic target for a subset of PTC. |
| first_indexed | 2024-03-09T05:48:41Z |
| format | Article |
| id | doaj.art-f6196e09150c4ba1bf769ca52f09ed40 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T05:48:41Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f6196e09150c4ba1bf769ca52f09ed402023-12-03T12:19:30ZengMDPI AGCancers2072-66942021-01-0113218510.3390/cancers13020185Prognostic Value and Function of KLF5 in Papillary Thyroid CancerPoyil Pratheeshkumar0Abdul K. Siraj1Sasidharan Padmaja Divya2Sandeep Kumar Parvathareddy3Sarah Siraj4Roxanne Diaz5Rafia Begum6Saif S. Al-Sobhi7Fouad Al-Dayel8Khawla S. Al-Kuraya9Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaHuman Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaHuman Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaHuman Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaHuman Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaHuman Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaHuman Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaDepartment of Surgery, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaDepartment of Pathology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi ArabiaHuman Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi ArabiaThe Krüppel-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in several solid tumors, but its role in PTC remains unclear. We investigated the expression of KLF5 protein in a large cohort of PTC patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. KLF5 overexpression was observed in 65.1% of all PTC cases and it was significantly associated with aggressive clinico-pathological parameters and poor outcome. Given the significant association between KLF5 and HIF-1α overexpression in PTC patients, we investigated the functional correlation between KLF5 and HIF-1α in PTC cells. Indeed, the analysis revealed the co-immunoprecipitation of KLF5 with HIF-1α in PTC cells. We also identified KLF5-binding sites in the HIF-1α promoter that specifically bound to KLF5 protein. Mechanistically, KLF5 promoted PTC cell growth, invasion, migration, and angiogenesis, while KLF5 downregulation via specific inhibitor or siRNA reverses its action in vitro. Importantly, the silencing of KLF5 decreases the self-renewal ability of spheroids generated from PTC cells. In addition, the depletion of KLF5 reduces PTC xenograft growth in vivo. These findings suggest KLF5 can be a possible new molecular therapeutic target for a subset of PTC.https://www.mdpi.com/2072-6694/13/2/185papillary thyroid cancerKLF5HIF-1αstemnessapoptosisinvasion |
| spellingShingle | Poyil Pratheeshkumar Abdul K. Siraj Sasidharan Padmaja Divya Sandeep Kumar Parvathareddy Sarah Siraj Roxanne Diaz Rafia Begum Saif S. Al-Sobhi Fouad Al-Dayel Khawla S. Al-Kuraya Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer Cancers papillary thyroid cancer KLF5 HIF-1α stemness apoptosis invasion |
| title | Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer |
| title_full | Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer |
| title_fullStr | Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer |
| title_full_unstemmed | Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer |
| title_short | Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer |
| title_sort | prognostic value and function of klf5 in papillary thyroid cancer |
| topic | papillary thyroid cancer KLF5 HIF-1α stemness apoptosis invasion |
| url | https://www.mdpi.com/2072-6694/13/2/185 |
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