Upregulation of CYP1B1-AS1 correlates with aggressive phenotypes and poor prognosis in thyroid cancer
摘要
Aberrant expression of lncRNA CYP1B1-AS1 drives the pathogenesis of diverse cancers, with thyroid carcinoma (TC) being no exception.
AimThis study was designed to clarify how CYP1B1-AS1 expression impacts prognostic outcomes in TC patients.
MethodsqRT-PCR was employed to measure CYP1B1-AS1 and miR-3127-5p expression signatures in TC tissues and cell lines. Prognostic value was analyzed by Kaplan-Meier survival and multivariate Cox regression assays. Binding affinities between CYP1B1-AS1/miR-3127-5p and miR-3127-5p/ERBB2 were validated by dual-luciferase reporter assays; RNA pull-down assays were used to confirm the CYP1B1-AS1/miR-3127-5p interaction. Flow cytometry, CCK-8, Wound Healing and Transwell assays were employed to evaluate TC cell apoptosis, growth, motility and invasiveness, respectively. Western blot was performed to detect ERBB2 protein expression.
ResultsCYP1B1-AS1 was significantly upregulated in TC tissues and cell lines, with concomitant downregulation of miR-3127-5p. TC patients with elevated CYP1B1-AS1 expression exhibited markedly decreased survival rates. CYP1B1-AS1, TNM stage, local invasion, and LNM were defined as prognostic correlates for TC. Knockdown of CYP1B1-AS1 inhibited the malignant phenotypic behaviors of TC cells. CYP1B1-AS1 bound to miR-3127-5p, and the miR-3127-5p inhibitor could counteract the inhibitory effects induced by CYP1B1-AS1 knockdown. ERBB2 was identified as a downstream target gene of miR-3127-5p.
ConclusionIncreased CYP1B1-AS1 expression correlates strongly with reduced overall survival in TC patients, establishing it as a clinically applicable prognostic indicator and promising therapeutic target.