Evaluation of t-DARPP Expression Alteration in Association with DDR1 Expression in Non-Small Cell Lung Cancer

Authors
Zahra Damavandi
Pardis Riahi
Tayebeh Majidizadeh
Massoud Houshmand
Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
10.61186/ibj.3878
Abstract
Background: Discoidin domain receptor 1 (DDR1) signaling plays a critical role in various cellular functions. Increased DDR1 expression has been shown in different human cancers. t-DARPP is a truncated isoform of DARPP-32, and its upregulation promotes cell survival and migration. Most lung cancer patients have non-small cell lung cancer (NSCLC), and their survival rate is low. Therefore, it is necessary to study new and effective targeted therapies. Increased t-DARPP expression in NSCLC patients is associated with patient survival and can act as a prognostic marker correlated with increasing stages of NSCLC. The current study aimed to evaluate alteration in DDR1 expression and its effects on t-DARPP expression in NSCLC.

Methods: Two human lung adenocarcinoma cell lines, A549 and Calu-3, were treated with collagen type I and transfected with DDR1 siRNA. The relative expression of DDR1 and t-DARPP was evaluated using qRT-PCR.

Results: The results indicated that collagen type I could stimulate DDR1 expression in NSCLC cells. Also, DDR1 upregulation resulted in a significant increase in t-DARPP expression. In contrast, suppression of DDR1 expression significantly decreased t-DARPP expression.

Conclusion: Our findings propose that modification in the expression of DDR1, caused by collagen type I and siRNA, might influence the expression of t-DARPP in NSCLC that is linked to NSCLC progression. Moreover, this alteration could potentially serve as an innovative target for therapeutic intervention.

Keywords
Collagen type I
Discoidin domain receptor 1
non-small cell lung cancer
Phosphoprotein phosphatase-1 regulatory subunit 1B