Long noncoding RNA BBOX1-AS1 increased radiotherapy sensitivity in colorectal cancer by stabilizing and activating PFK1

长链非编码RNA BBOX1-AS1通过稳定和激活PFK1,提高了结直肠癌对放射治疗的敏感性。

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作者:Qi Wang,Xiao-Fei Li,Ying-Hui Zhou,Xiang-Hong Qin,Li-Hui Wang,Meng-Qing Xiao,Ke Cao,John K Ma,Cheng-Hui Huang

Abstract

Purpose: Our study explored the effect of long noncoding RNA BBOX1-AS1 on colorectal cancer (CRC) radiosensitivity in vivo and in vitro. Methods: Differentially expressed lncRNAs in CRC were screened using a bioinformatics database and an online prediction website. The expression of BBOX1-AS1 in tissue samples was analyzed via real-time quantitative PCR (RT-qPCR). Subcellular localization of BBOX1-AS1 in CRC cells was analyzed using fluorescence in situ hybridization (FISH). The correlation between BBOX1-AS1 and PFK1 expression levels in CRC tissues was analyzed via Pearson's correlation coefficient. The effect of BBOX1-AS1 on PFK1 stability was investigated using RNA and protein stability testing. RNA Binding Protein Immunoprecipitation (RIP) and RNA pull-down assays were used to confirm the binding of BBOX1-AS1 to PFK1. Results: BBOX1-AS1 was highly expressed in CRC and associated with poor prognosis. Similarly, it was highly expressed in CRC tissues and CRC cell lines. In addition, BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells and inhibited apoptosis. RIP and RNA pull-down experiments confirmed that BBOX1-AS1 bound to PFK1. RNA stability and protein stability experiments showed that BBOX1-AS1 affected the stability of PFK1 mRNA and protein. Furthermore, we confirmed that BBOX1-AS1 increased radiation resistance through the regulation of PFK1 expression. Conclusions: BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells through stabilization of the expression of PFK1. BBOX1-AS1 also inhibited CRC cell apoptosis and increased radiotherapy resistance in CRC cells.

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