Prakash Anand, Patel Yashvant, Roy Jagat Kumar
Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
Department of Zoology, SVP College, Bhabua (Kaimur), 821101, India.
Genes Genomics. 2025 Apr;47(4):487-501. doi: 10.1007/s13258-025-01620-3. Epub 2025 Jan 28.
Cervical cancer is the fourth most common cancer worldwide in females. This occurs primarily due to the infection of high-risk Human Papilloma Virus (HPV), although in advanced stages it requires support from host cellular factors. BRN3A is one such host cellular factors, whose expression remains high in cervical cancers and upregulates tumorigenic HPV gene expression. The effect of BRN3A on HPV-mediated cervical cancer and the underlying mechanism remains obscure.
To investigates the effect of BRN3A on cancer-promoting biological processes in HPV-positive uterine cervix cancer cells.
We have altered the expression of BRN3A through over-expression (OE) and knock-down (KD) constructs in cervical cancer cell line, SiHa, and did transcriptome profiling through next-generation RNA-sequencing, validation through RT-PCR and BRN3A binding study with in silico promoter study and ChIP PCR methods.
This study revealed a substantial change in the expression of several genes associated with cancer-promoting biological processes including viral processes, immune response, cell-death, cell-proliferation, different signaling pathways, etc. Additionally, promoter analysis through in silico mode revealed that a total of 32.7% of genes possess BRN3A binding sites at their promoters. Physical interaction of BRN3A with IFITM1, OAS3, ISG15, BCL2L1 and HSP90AB1 genes was also confirmed.
The present study identified molecular targets of BRN3A and provided new insight into the pathogenesis of cervical cancer. According to our knowledge, this is the first report on the effect on eukaryotic transcriptomes after over-expression and knocking down BRN3A.
宫颈癌是全球女性中第四大常见癌症。其主要由高危型人乳头瘤病毒（HPV）感染引起，不过在晚期阶段，它需要宿主细胞因子的支持。BRN3A就是这样一种宿主细胞因子，其在宫颈癌中的表达仍然很高，并且会上调致癌性HPV基因的表达。BRN3A对HPV介导的宫颈癌的影响及其潜在机制仍不清楚。
研究BRN3A对HPV阳性子宫颈癌细胞中促进癌症生物学过程的影响。
我们通过在宫颈癌细胞系SiHa中过表达（OE）和敲低（KD）构建体来改变BRN3A的表达，并通过下一代RNA测序进行转录组分析，通过RT-PCR进行验证，并使用计算机模拟启动子研究和ChIP PCR方法进行BRN3A结合研究。
本研究揭示了与促进癌症生物学过程相关的几个基因的表达发生了重大变化，包括病毒过程、免疫反应、细胞死亡、细胞增殖、不同的信号通路等。此外，通过计算机模拟模式进行的启动子分析表明，共有32.7%的基因在其启动子处具有BRN3A结合位点。还证实了BRN3A与IFITM1、OAS3、ISG15、BCL2L1和HSP90AB1基因的物理相互作用。
本研究确定了BRN3A的分子靶点，并为宫颈癌的发病机制提供了新的见解。据我们所知，这是关于过表达和敲低BRN3A后对真核转录组影响的第一份报告。
