The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis
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Cancer Cell International Open Access
PRIMARY RESEARCH
The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR‑497‑5p/ FOXK1 axis Nan Wang, Jia‑Xing He, Guo‑Zhan Jia, Ke Wang, Shuai Zhou, Tao Wu* and Xian‑Li He*
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 deter‑ mined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was deter‑ mined 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 inva‑ sion. Silencing of XIST also reversed the downregulation of miR-497-5p and upregulation of FOXK1. Moreover, block‑ ing 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. Keywords: LncRNA XIST, miR-497-5p, FOXK1, Colon cancer cell carcinoma Background Colorectal cancer (CRC) is a common malignancy, accounting for 9.2% of all cancers [1], with lower incidence seen in developed countries, relative to those with less developed economies [2]. Despite substantial progress in surgical techniques and other anti-cancer treatments, treatment outcomes for CRC have not significantly improved. Surgery remains the only proven
*Correspondence: [email protected]; [email protected] Department of General Surgery, Tangdu Hospital, the Air Force Medical University, 710038 Xi’an, China
curative treatment for CRC; however, such treatments are not possible for the majority of patients with advanced CRC [3]. The development of new treatment options is therefore urgently needed to address these unmet needs [4]. To achieve these goals, we will need a better understanding of the molecular mechanisms underlying CRC pathogenesis to improve both the diagnosis and treatment of CRC. Long non-coding RNAs (lncRNAs) are a newly discovered class of RNA molecules that are typically over 200 nt in length. LncRNAs have been sho
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