Yuehua Li1,2,3,4,5,6,7, Wen Shi2,3,4,5,6,7,8, Yajun Shen1,2,3,4,5,6,7, Li Xu1,2,3,4,5,6,7, Zhigang Cai1,2,3,4,5,6,7, Xiaofeng Shan1,2,3,4,5,6,7. 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China. 2. National Center of Stomatology, Beijing, China. 3. National Clinical Research Center for Oral Diseases, Beijing, China. 4. National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China. 5. Beijing Key Laboratory of Digital Stomatology, Beijing, China. 6. Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, Beijing, China. 7. NMPA Key Laboratory for Dental Materials, Beijing, China. 8. First Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China.
Abstract
Background: Krüppel-like factor 5 (KLF5) is highly expressed in a variety of tumors, and our study aimed to investigate the role of KLF5 in oral squamous cell carcinoma (OSCC). Methods: To explore the differential expression of KLF5, next-generation sequencing (NGS) and further analyses were conducted in paired premalignant and tumor tissues and adjacent normal mucosa. We then analyzed the mRNA expression data from The Cancer Genome Atlas (TCGA) and performed gene set enrichment analysis (GSEA) to predict the function of KLF5. Small interfering RNA (siRNA) targeting KLF5 was used to knock down its expression in cells and further evaluate the changes in cell apoptosis, proliferation, and migration. We predicted whether baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) was the potential target gene of KLF5 via the NCBI and JASPAR databases. Furthermore, we analyzed BIRC5 expression after KLF5 knockdown and explored its function in athymic BALB/c nude mice. Results: KLF5 expression in clinical samples gradually increased from normal mucosa tissues to premalignant and then to OSCC tissues. Analysis of TCGA data and GSEA also suggested that KLF5 was expressed at higher levels in OSCC and involved apoptosis and the protein 53 (P53), transforming growth factor-β (TGF-β), and wingless/integrated (Wnt) signaling pathways. Cell apoptosis was promoted, whereas proliferation and migration were inhibited after KLF5 knockdown. Furthermore, we found KLF5 transcription binding sites on the BIRC5 promoter and BIRC5 expression was inhibited after suppressing KLF5 in vitro and in vivo. Conclusions: Our findings indicate that KLF5 promotes the development of OSCC via BIRC5, and could be a potential diagnostic and therapeutic target for OSCC. 2022 Annals of Translational Medicine. All rights reserved.
Background: Krüppel-like factor 5 (KLF5) is highly expressed in a variety of tumors, and our study aimed to investigate the role of KLF5 in oral squamous cell carcinoma (OSCC). Methods: To explore the differential expression of KLF5, next-generation sequencing (NGS) and further analyses were conducted in paired premalignant and tumor tissues and adjacent normal mucosa. We then analyzed the mRNA expression data from The Cancer Genome Atlas (TCGA) and performed gene set enrichment analysis (GSEA) to predict the function of KLF5. Small interfering RNA (siRNA) targeting KLF5 was used to knock down its expression in cells and further evaluate the changes in cell apoptosis, proliferation, and migration. We predicted whether baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) was the potential target gene of KLF5 via the NCBI and JASPAR databases. Furthermore, we analyzed BIRC5 expression after KLF5 knockdown and explored its function in athymic BALB/c nude mice. Results: KLF5 expression in clinical samples gradually increased from normal mucosa tissues to premalignant and then to OSCC tissues. Analysis of TCGA data and GSEA also suggested that KLF5 was expressed at higher levels in OSCC and involved apoptosis and the protein 53 (P53), transforming growth factor-β (TGF-β), and wingless/integrated (Wnt) signaling pathways. Cell apoptosis was promoted, whereas proliferation and migration were inhibited after KLF5 knockdown. Furthermore, we found KLF5 transcription binding sites on the BIRC5 promoter and BIRC5 expression was inhibited after suppressing KLF5 in vitro and in vivo. Conclusions: Our findings indicate that KLF5 promotes the development of OSCC via BIRC5, and could be a potential diagnostic and therapeutic target for OSCC. 2022 Annals of Translational Medicine. All rights reserved.
Authors: Beth B McConnell; Samuel S Kim; Ke Yu; Amr M Ghaleb; Norifumi Takeda; Ichiro Manabe; Asma Nusrat; Ryozo Nagai; Vincent W Yang Journal: Gastroenterology Date: 2011-07-18 Impact factor: 22.682