Abstract
BackgroundColorectal cancer (CRC) is the fourth most deadly malignancy throughout the world. Extensive studies have shown that Krüppel-like factors (KLFs) play essential roles in cancer development. However, the function of KLF13 in CRC is unclear.MethodsThe Cancer Genome Atlas database was applied to analyze the expression of KLF13 in CRC and normal tissues. Lentivirus system was used to overexpress and to knock down KLF13. RT-qPCR and Western blot assays were performed to detect mRNA and protein expression. CCK-8, colony formation, cell cycle analysis and EdU staining were used to assess the in vitro function of KLF13 in CRC cells. Xenografter tumor growth was used to evaluate the in vivo effect of KLF13 in CRC. Cholesterol content was measured by indicated kit. Transcription activity was analyzed by luciferase activity measurement. ChIP-qPCR assay was performed to assess the interaction of KLF13 to HMGCS1 promoter.ResultsKLF13 was downregulated in CRC tissues based on the TCGA database and our RT-qPCR and Western blot results. Comparing with normal colorectal cells NCM460, the CRC cells HT-26, HCT116 and SW480 had reduced KLF13 expression. Functional experiments showed that KLF13 knockdown enhanced the proliferation and colony formation in HT-29 and HCT116 cells. Opposite results were observed in KLF13 overexpressed cells. Furthermore, KLF13 overexpression resulted in cell cycle arrest at G0/G1 phase, reduced EdU incorporation and suppressed tumor growth of HCT116 cells in nude mice. Mechanistically, KLF13 transcriptionally inhibited HMGCS1 and the cholesterol biosynthesis. Knockdown of HMGCS1 suppressed cholesterol biosynthesis and the proliferation of CRC cells with silenced KLF13. Furthermore, cholesterol biosynthesis inhibitor significantly retarded the colony growth in both cells.ConclusionsOur study reveals that KLF13 acts as a tumor suppressor in CRC through negatively regulating HMGCS1-mediated cholesterol biosynthesis.
Highlights
Colorectal cancer (CRC) is the fourth most deadly malignancy throughout the world
KLF13 is downregulated in colorectal cancer (CRC) tissues To investigate the clinical relevance of KLF13 in CRC, we collected the TCGA database and analyzed the KLF13 in CRC tissues
We found that KLF13 transcript was decreased in CRC tissues as compared with the normal tissues (Fig. 1a)
Summary
Colorectal cancer (CRC) is the fourth most deadly malignancy throughout the world. Extensive studies have shown that Krüppel-like factors (KLFs) play essential roles in cancer development. The well known risk factors for CRC include obesity, smoking, gut microbiota and genetic variants [3, 4]. These factors contact with each other to cause the formation of CRC. Krüppel-like factors (KLFs), which are zinc-finger transcription factors, regulate the expression of various substrates [5]. Based on their transcription activity, KLF1–17 are divided into two different groups: (1) KLF1, 2, 4, 5, 6 and 7 act as ‘activator’; (2) the remaining functions as ‘repressor’. KLF13 gene is located at the chromosome 15 It is overexpressed in oral cancer cells.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
