Abstract:
The bacterial spirochete Borrelia burgdorferi, the causative agent of Lyme Disease, can disseminate and colonize various tissues and organs, orchestrating severe clinical symptoms including arthritis, carditis, and neuroborreliosis. Previous research has demonstrated that breast cancer tissues could provide an ideal habitat for diverse populations of bacteria, including B. burgdorferi, which is associated with a poor prognosis. Recently, we demonstrated that infection with B. burgdorferi enhances the invasion and migration of triple-negative MDA-MB-231 cells which represent a type of breast tumor with more aggressive cancer traits. In this study, we hypothesized that infection by B. burgdorferi affects the expression of cancer-associated genes to effectuate breast cancer phenotypes. We applied the high-throughput technique of RNA-sequencing on B. burgdorferi-infected MDA-MB-231 breast cancer and normal-like MCF10A cells to determine the most differentially expressed genes (DEG) upon infection. Overall, 142 DEGs were identified between uninfected and infected samples in MDA-MB-231 while 95 DEGs were found in MCF10A cells. A major trend of the upregulation of C-X-C and C-C motif chemokine family members as well as genes and pathways was associated with infection, inflammation, and cancer. These genes could serve as potential biomarkers for pathogen-related tumorigenesis and cancer progression which could lead to new therapeutic opportunities.
摘要:
细菌螺旋体伯氏螺旋体,莱姆病的病原体,可以传播和定植各种组织和器官,协调包括关节炎在内的严重临床症状,心脏炎,和神经性伯利松病。先前的研究表明,乳腺癌组织可以为不同的细菌种群提供理想的栖息地,包括B.Burgdorferi,这与预后不良有关。最近,我们证明,B.burgdorferi感染可增强三阴性MDA-MB-231细胞的侵袭和迁移,而MDA-MB-231细胞是一种具有更具侵袭性的乳腺肿瘤.在这项研究中,我们假设B.burgdorferi感染会影响癌症相关基因的表达,从而影响乳腺癌的表型.我们将RNA测序的高通量技术应用于B.burgdorferi感染的MDA-MB-231乳腺癌和正常样MCF10A细胞,以确定感染后最差异表达的基因(DEG)。总的来说,在MDA-MB-231中的未感染和感染样品之间鉴定了142个DEGs,而在MCF10A细胞中发现了95个DEGs。C-X-C和C-C基序趋化因子家族成员以及基因和通路上调的主要趋势与感染有关。炎症,和癌症。这些基因可以作为病原体相关肿瘤发生和癌症进展的潜在生物标志物,这可能导致新的治疗机会。