长链非编码RNA BBOX1-AS1通过稳定和激活磷酸果糖激酶1（PFK1）提高结直肠癌的放疗敏感性。

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

作者信息

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

机构信息

Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.

Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; The Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital) , Chengdu, 610051, Sichuan, China.

出版信息

Transl Oncol. 2023 Oct;36:101751. doi: 10.1016/j.tranon.2023.101751. Epub 2023 Aug 4.

DOI:10.1016/j.tranon.2023.101751

PMID:37544035

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10423889/

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.

摘要

目的

本研究探讨长链非编码RNA BBOX1-AS1在体内和体外对结直肠癌（CRC）放射敏感性的影响。

方法

利用生物信息学数据库和在线预测网站筛选CRC中差异表达的长链非编码RNA。通过实时定量PCR（RT-qPCR）分析组织样本中BBOX1-AS1的表达。使用荧光原位杂交（FISH）分析CRC细胞中BBOX1-AS1的亚细胞定位。通过Pearson相关系数分析CRC组织中BBOX1-AS1与PFK1表达水平之间的相关性。使用RNA和蛋白质稳定性测试研究BBOX1-AS1对PFK1稳定性的影响。采用RNA结合蛋白免疫沉淀（RIP）和RNA下拉实验来确认BBOX1-AS1与PFK1的结合。

结果

BBOX1-AS1在CRC中高表达且与预后不良相关。同样，它在CRC组织和CRC细胞系中也高表达。此外，BBOX1-AS1促进CRC细胞的增殖、侵袭、迁移和糖酵解，并抑制细胞凋亡。RIP和RNA下拉实验证实BBOX1-AS1与PFK1结合。RNA稳定性和蛋白质稳定性实验表明BBOX1-AS1影响PFK1 mRNA和蛋白质的稳定性。此外，我们证实BBOX1-AS1通过调节PFK1表达增加放射抗性。