Fernandez-Avila Leonardo, Castro-Amaya Aribert Maryosly, Molina-Pineda Andrea, Hernández-Gutiérrez Rodolfo, Jave-Suarez Luis Felipe, Aguilar-Lemarroy Adriana
Programa de Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico.
Biomedicines. 2023 Sep 28;11(10):2655. doi: 10.3390/biomedicines11102655.
Cervical cancer (CC) is a serious global health issue, and it is well-known that HPV infection is the main etiological factor that triggers carcinogenesis. In cancer, chemokine ligands and receptors are involved in tumor cell growth, metastasis, leukocyte infiltration, and angiogenesis; however, information on the role played by E6/E7 of HPV16/18 in the modulation of chemokines is very limited. Therefore, this study aimed to determine whether chemokines are differentially expressed in CC-derived cell lines; if E6/E7 oncoproteins from HPV16 and 18 are capable of mediating chemokine expression, what is the expression profile of chemokines in tissues derived from CC and what is their impact on the overall survival of patients with this pathology? For this purpose, RNA sequencing and real-time PCR were performed on SiHa, HeLa, and C33A tumorigenic cell lines, on the non-tumorigenic HaCaT cells, and the HPV-transduced HaCaT cell models. Furthermore, chemokine expression and survival analysis were executed on 304 CC and 22 normal tissue samples from The Cancer Genome Atlas (TCGA) repository. The results demonstrate that , , , and are regulated by of HPV16 and 18, are overexpressed in CC biopsies, and that their higher expression is related to a worse prognostic survival.
宫颈癌（CC）是一个严重的全球健康问题，众所周知，人乳头瘤病毒（HPV）感染是引发癌变的主要病因。在癌症中，趋化因子配体和受体参与肿瘤细胞生长、转移、白细胞浸润及血管生成；然而，关于HPV16/18的E6/E7在趋化因子调节中所起作用的信息非常有限。因此，本研究旨在确定趋化因子在CC衍生细胞系中是否差异表达；如果来自HPV16和18的E6/E7癌蛋白能够介导趋化因子表达，那么趋化因子在CC衍生组织中的表达谱是怎样的，以及它们对这种病理状况患者的总生存期有何影响？为此，对SiHa、HeLa和C33A致瘤细胞系、非致瘤性HaCaT细胞以及HPV转导的HaCaT细胞模型进行了RNA测序和实时PCR。此外，对来自癌症基因组图谱（TCGA）数据库的304份CC组织样本和22份正常组织样本进行了趋化因子表达和生存分析。结果表明， 、 、 和 受HPV16和18的 调控，在CC活检组织中过表达，且其较高表达与较差的预后生存相关。
