RETRACTED ARTICLE: The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis

Nan Wang,Ke Wang,Jia Xing He ,Shuai Zhou,Guo-Zhan Jia,Xian-Li He,Tao Wu,Jia-Xing He,Shuai Xhou,Xian Li He

doi:10.1186/s12935-020-01647-4

Nan Wang, Ke Wang + Show 8 more

Open Access

https://doi.org/10.1186/s12935-020-01647-4

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Abstract

BackgroundRecent 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.MethodsExpression 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.ResultsXIST 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.ConclusionsXIST 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.

Highlights

CFeOlXl gKr1oawxtihs through regulating the miR‐497‐5pE/ Nan Wang, Jia‐Xing He, Guo‐Zhan Jia, Ke Wang, Shuai Zhou, Tao Wu* and Xian‐Li He* CL Abstract I Background: Recent studies suggest that long noncoding RNAs play an important role in tumorigenesis
D ing X-Inactive Specific Transcript (XIST) expression was shown to inhibit colorectal cancer (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 targeted forkhead box k1 (FOXK1) in CRC cells
E 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

Summary

Results

R qPCR was used to measure XIST expression in CRC tissues and cells. XIST expression was shown to be sig-. FOXK1 protein expression was significantly inhibited by XIST silencing in HT29 and SW480 cells (Fig. 6a). (Fig. 5c) and protein expression (Fig. 5d) in CRC tissues sion were suppressed in the si-XIST group, but the and cell lines compared with normal controls (Fig. 5e). FOXK1 protein expression was deter- group, as determined using the Transwell assay (Fig. 6d, mined to be markedly inhibited after miR-497-5p over- e). Together, these results indicate that FOXK1 may expression, which was restored by overexpression of promote the progression of colon cancer cells and that. XIST was transfected into CRC cells, it led to an increase sion on proliferation, anti-apoptosis activity, and metasin miR-497-5p expression, thereby arresting colon can- tasis in CRC cells. Sarogni P, Palumbo O, Servadio A, Astigiano S, D’Alessio B, Gatti V, Cukrov

E Conclusions

E Sample collection

A Cell culture and transfection

E Statistical analysis

Conclusions

Competing interest