Global transcriptomic analysis of breast cancer and normal mammary epithelial cells infected with Borrelia burgdorferi.

European journal of microbiology & immunology Pub Date : 2023-10-19 Print Date: 2023-11-23 DOI:10.1556/1886.2023.00031
Vishwa A Khatri, Sambuddha Paul, Niraj Jatin Patel, Sahaja Thippani, Janhavi Y Sawant, Katie L Durkee, Cassandra L Murphy, Geneve Ortiz Aleman, Justine A Valentino, Jasmine Jathan, Anthony Melillo, Eva Sapi
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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.

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伯氏疏螺旋体感染的癌症和正常乳腺上皮细胞的全转录组学分析。
细菌螺旋体伯氏疏螺旋体是莱姆病的病原体,可在各种组织和器官中传播和定植,引发严重的临床症状,包括关节炎、心肌炎和神经相关疾病。先前的研究表明,癌症组织可以为包括伯氏菌在内的多种细菌提供理想的栖息地,这与预后不良有关。最近,我们证明伯氏疟原虫感染增强了三阴性MDA-MB-231细胞的侵袭和迁移,这是一种具有更具侵袭性癌症特征的乳腺肿瘤。在这项研究中,我们假设伯氏疟原虫感染会影响癌症相关基因的表达,从而实现乳腺癌症表型。我们将RNA测序的高通量技术应用于B.burgdorferi感染的MDA-MB-231乳腺癌症和正常样MCF10A细胞,以确定感染时差异表达最多的基因(DEG)。总体而言,在MDA-MB-231中,在未感染和感染的样本之间鉴定出142个DEG,而在MCF10A细胞中发现95个DEG。C-X-C和C-C基序趋化因子家族成员以及基因和途径上调的主要趋势与感染、炎症和癌症有关。这些基因可以作为与病因相关的肿瘤发生和癌症进展的潜在生物标志物,这可能会带来新的治疗机会。
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