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LncRNA XIST sponges microRNA-448 to promote malignant behaviors of colorectal cancer cells via regulating GRHL2

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Abstract

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential regulators in human cancers, while the role of lncRNA X-inactive-specific transcript (XIST) in colorectal cancer (CRC) via regulating miR-448 remains largely unknown. Herein, we aimed to elucidate the effect of the XIST/miR-448/grainyhead-like 2 (GRHL2) axis on CRC development. XIST, miR-448, and GRHL2 expression in CRC tissues from patients and in human CRC cell lines was assessed. Loss- and gain-function assays were implemented to unveil the roles of XIST, miR-448, and GRHL2 in screened CRC cells. The tumor growth in vivo was observed in nude mice. Binding relations among XIST, miR-448, and GRHL2 were evaluated. XIST and GRHL2 expressed highly whereas miR-448 expressed lowly in CRC tissues and cells. XIST or GRHL2 downregulation, or miR-448 elevation suppressed the malignant behaviors of CRC cells in vitro, and downregulated XIST or upregulated miR-448 also inhibited the tumor growth in vivo. miR-448 upregulation reversed the role of XIST elevation in CRC cells. XIST particularly bound to miR-448, and miR-448 targeted GRHL2. Knockdown of XIST upregulates miR-448 to impede malignant behaviors of CRC cells via inhibiting GRHL2. This study may provide novel biomarkers for CRC diagnosis and treatment.

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Funding

This study was funded by Shanxi Province “136 Revitalization Medical Project Construction Funds”.

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Authors and Affiliations

  1. General Surgery Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 LongCheng Street, Taiyuan, 030001, Shanxi, China

    Zhengzheng Yan, Ji Li, Ji Guo & Ruochong He

  2. Department of Breast Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 LongCheng Street, Taiyuan, 030001, Shanxi, China

    Jun Xing

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  1. Zhengzheng Yan
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  2. Ji Li
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  3. Ji Guo
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  4. Ruochong He
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  5. Jun Xing
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Correspondence to Jun Xing.

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Yan, Z., Li, J., Guo, J. et al. LncRNA XIST sponges microRNA-448 to promote malignant behaviors of colorectal cancer cells via regulating GRHL2. Funct Integr Genomics 22, 977–988 (2022). https://doi.org/10.1007/s10142-022-00873-5

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  • DOI: https://doi.org/10.1007/s10142-022-00873-5

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