Downregulation of PDIA3 inhibits proliferation and invasion of human acute myeloid leukemia cells

Abstract

IntroductionAcute myeloid leukemia (AML) is a common malignancy of the hematopoietic system. In bone marrow samples of AML patients, PDIA3 expression was higher than that in the samples of healthy controls. We aimed at exploring the effect of PDIA3 siRNA on proliferation, apoptosis, migration, and invasion of AML HL-60 and HEL cells.Materials and methodsRT-PCR was performed to identify PDIA3 expression. Cell proliferation was assessed by MTT. Flow cytometry analysis and transwell were used to detect cell apoptosis, migration and invasion. Gene set enrich-ment analysis (GSEA) was employed to explore the PDIA 3-associated pathways in AML. Western blotting was used for protein expression detection.ResultsPDIA3 siRNA significantly inhibited the proliferation of AML cells at 24 and 48 h. PDIA3 siRNA notably enhanced the percentage of apoptotic cells. The migration and invasion abilities of HL-60 and HEL cells in the PDIA3 siRNA group were significantly suppressed compared with those in the control and siNC groups. GSEA of the Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways could be correlated with PDIA3 expression; this was further confirmed in AML cells by Western blotting. MAPK signaling was also blocked by PDIA3 siRNA.ConclusionPDIA3 siRNA effectively enhanced apoptosis, and suppressed proliferation, invasion, and migration of AML cells by regulating oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways, and MAPK signaling, which can provide novel therapeutic targets for AML.

Identification of a novel Protein Disulfide-isomerase A3 (PDIA3) transcript variant as a potential biomarker associated with late stage prostate cancer

“…Previous studies pinpoint PDIA3 as a plausible candidate for studying cancer prognosis and as a target for cancer treatment (19)(20)(21)(22)31). The role of PDIA3 in cancer treatment remains controversial and the implication of different PDIA3 transcript isoforms has not yet been studied in connection with prostate cancer progression.…”

“…These actions include the regulation of intracellular, extranuclear pathways and signaling cascades, such as the activation of the protein kinase C (PKC) pathway and the calcium transport (16). The role of PDIA3 in cancer regulation remain controversial since some studies suggest that it is responsible of the activation of proapoptotic pathways (19,20) and other studies that it is associated with cancer proliferation, inhibition of the apoptosis and poor prognosis (21,22). VDR was found to be lower expressed in prostate tissue while PDIA3 was higher expressed at protein and transcript level in both normal and cancer prostate tissue (23).…”

Identification of a novel Protein Disulfide-isomerase A3 (PDIA3) transcript variant as a potential biomarker associated with late stage prostate cancer

“…Previous studies pinpoint PDIA3 as a plausible candidate for studying cancer prognosis and as a target for cancer treatment (19)(20)(21)(22)31). The role of PDIA3 in cancer treatment remains controversial and the implication of different PDIA3 transcript isoforms has not yet been studied in connection with prostate cancer progression.…”

Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer

“…These actions include regulation of intracellular, extranuclear pathways and signaling cascades, such as the activation of the protein kinase C (PKC) pathway and the calcium transport [13]. The role of PDIA3 in cancer regulation remains controversial since some studies suggest that it is responsible for the activation of proapoptotic pathways [18,19] whereas others suggest association with cancer proliferation, inhibition of apoptosis and poor prognosis [20,21]. In both normal and cancer prostate tissues, VDR is found to be lower both at level of transcription and translation compared to PDIA3 [22].…”