ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2023
The involvement of PDIA2 gene in the progression of renal cell carcinoma is potentially through regulation of JNK signaling pathway.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
Renal cell carcinoma (RCC) with poor prognosis and high incidence rate is a common malignant disease. Current therapies could bring little benefit for the patients with advanced-stage RCC. PDIA2 is an isomerase responsible for protein folding and its role in cancer including RCC is under investigation. In this study, we found that PDIA2 was expressed much higher in RCC tissues than the control but the methylation level of PDIA2 promoter was lower based on the TCGA data. Patients with higher PDIA2 expression exerted worse survival. In clinical specimen, PDIA2 expression was correlated to patients' clinical factors such as TNM stage (I/II vs III/IV, p = 0.025) and tumor size (≤ 7 cm vs > 7 cm, p = 0.004). Moreover, K-M analysis showed that PDIA2 was associated with patients' survival in RCC. PDIA2 was expressed much higher in cancer cells A498 than 786-O than that in 293 T cells. After PDIA2 was knocked down, cell proliferation, migration and invasion was potently inhibited. But cell apoptotic rate increased reversely. Furthermore, the efficacy of Sunitinib on RCC cells was strengthened after PDIA2 knockdown. In addition, knockdown of PDIA2 gene leaded to downregulation of levels of JNK1/2, phosphorylated JNK1/2, c-JUN, and Stat3. But this inhibition was partially released when JNK1/2 was overexpressed. In consistent, cell proliferation was also partially recovered. In summary, PDIA2 plays important role in progression of RCC and JNK signaling pathway might be regulated by PDIA2. This study suggests PDIA2 as a candidate target for therapy of RCC.
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