The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis

Cancer Cell International

Ke Wang¹  Shuai Zhou¹  Guo-Zhan Jia¹  Xian-Li He¹  Jia-Xing He¹  Tao Wu¹  Nan Wang¹ 

[1] Department of General Surgery, Tangdu Hospital, the Air Force Medical University;

关键词: LncRNA XIST;    miR-497-5p;    FOXK1;    Colon cancer cell carcinoma;   

DOI  :  10.1186/s12935-020-01647-4

来源: DOAJ

【 摘 要 】

Abstract Background Recent studies suggest that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. As a newly identified lncRNA, the role of XIST in colorectal cancer (CRC) has not been established. Here, we sought to characterize the role of XIST and its associated regulatory network in CRC cells. Methods Expression of XIST mRNA, miR-497-5p, and forkhead box k1 (FOXK1) in CRC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of CRC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between XIST, miR-497-5p, and FOXK1 were predicted and confirmed using a dual-luciferase reporter assay. Expression of FOXK1 protein was quantified by Western blot. Results XIST and FOXK1 expression were significantly upregulated in CRC tissues and cell lines, while miR-497-5p expression was downregulated. XIST knockdown significantly suppressed CRC cell proliferation, migration, and invasion. Silencing of XIST also reversed the downregulation of miR-497-5p and upregulation of FOXK1. Moreover, blocking XIST expression was shown to inhibit CRC tumor growth in vivo and the effects were antagonized by the loss of miR-497-5p. miR-497-5p was shown to act as a sponge of XIST and also targeted FOXK1 in CRC cells. Conclusions XIST was shown to promote the malignancy of CRC cells by competitively binding to miR-497-5p, resulting in an increase in FOXK1 expression. These results suggest that targeting of XIST may represent a possible treatment for CRC.

【 授权许可】

Unknown