CXCL13 is androgen-responsive and involved in androgen induced prostate cancer cell migration and invasion

Abstract

Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues. In cultures, expression of CXCL13 is up-regulated by androgen-AR axis at both mRNA and protein levels. Furthermore, Chip-Seq assay identifies canonical androgen responsive elements (ARE) at CXCL13 enhancer and dual-luciferase reporter assays reveals that the ARE is highly responsive to androgen while mutations of the ARE abolish the reporter activity. Additional chromatin immunoprecipitation (ChIP) assays also identify that the ARE presents androgen responsiveness. In addition, CXCL13 promotes G2/M phase transition by increasing Cyclin B1 levels in PCa cells. Functional studies demonstrate that reducing endogenous CXCL13 expression in LNCaP cells largely weakens androgen-AR axis induced cell migration and invasion. Taken together, our study implicates for the first time that CXCL13 is an AR target gene and involved in AR-mediated cell migration and invasion in primary PCa.

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

“…1B). Among them, SPP1 [19], GCNT3 [11], TMPRSS4 [20], SPINK1 [21], HABP2 [22], and CXCL13 [23] are known oncogenes for tumor i-genesis, while two, namely TMPRSS4 and HABP2, were identified as oncogenes in lung cancer. The top 10 up-regulated mRNAs in NSCLC tissues are listed in Table 2.…”

Gastric Damage and Cancer-Associated Biomarkers in Helicobacter pylori-Infected Children

“…Overexpression of CXCL9 and 10 is found in GC tissue compared to normal gastric tissue (Raja et al, 2017), however, data on CXCL11 expression in GC was not found. CXCL13 (C-X-C motif chemokine ligand 13) is related to cell proliferation and associated with poor prognosis in several neoplasms, including GC (Fan et al, 2017;Wei et al, 2018). Obayashi et al (2016) showed CXCL13 overexpression primarily around lymphoid follicles in gastric biopsies from infected children; while Ikuse et al (2012) showed overexpression of CXCL9, 10, 11, 13, and CCL18 in gastric tissue of infected children, all of whom had histological inflammation and nodular gastritis.…”

Characterization of the Immune Response in Patients Infected with Clostridioides Difficile Due to Serum Biomarkers' Level with Correlation to Clinical Characteristics and Bacterial Toxin Production

“…According to this score, CDI patients were divided into groups of mild to moderate disease and severe disease using a severity score index according to the guidelines of the "Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America" (SHEA-IDSA) as follows: mild to moderate disease¼leukocytosis ≤ 15,000 cells/ml and creatinine ≤ 1.5 times the premorbid level; severe disease ¼ leukocytosis ≥ 15,000 cells/ml or serum creatinine ≥ 1.5 times the premorbid level. Severe disease was de ned also as a serum albumin level of ≤ 3 g/dl at the time of active infection [22,23].…”