KLF13 suppresses the proliferation and growth of colorectal cancer cells through transcriptionally inhibiting HMGCS1-mediated cholesterol biosynthesis

Background Colorectal cancer (CRC) is the fourth most deadly malignancy throughout the world. Extensive studies have shown that Kruppel-like factors (KLFs) play essential roles in cancer development. However, the function of KLF13 in CRC is unclear. Methods The 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. Results KLF13 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. Conclusions Our study reveals that KLF13 acts as a tumor suppressor in CRC through negatively regulating HMGCS1-mediated cholesterol biosynthesis.