Basic Information
LncRNA/CircRNA Name | PDIA3P1 |
Synonyms | NA |
Region | NA |
Ensemble | NA |
Refseq | NA |
Classification Information
Regulatory Mechanism | Biological Function | Clinical Application | |||
---|---|---|---|---|---|
TF | Immune | Survival | |||
Enhancer | Apoptosis | apoptosis | Drug | Dox | |
Variant | Cell Growth | Circulating | 2 | ||
MiRNA | EMT | Metastasis | |||
Methylation | Coding Ability | Recurrence |
Cancer&Entry Information
Cancer Name | hepatocellular carcinoma |
ICD-0-3 | C22.0 |
Methods | qPCR, Western blot, Luciferase reporter assay, RIP, etc. |
Sample | HCC tissues, hepatoma cell lines (SK-Hep-1, QGY-7703) |
Expression Pattern | up-regulated |
Function Description | Higher PDIA3P1 level was associated with poorer recurrence-free survival of human hepatocellular carcinoma (HCC). Both gain- and loss-of-function studies revealed that PDIA3P1 protected cancer cells from Dox-induced apoptosis and allowed tumor xenografts to grow faster and to be more resistant to Dox treatment. Mechanistically, miR-125a/b and miR-124 suppressed the expression of tumor necrosis factor receptor associated factor 6 (TRAF6), but PDIA3P1 bound to miR-125a/b/miR-124 and relieved their repression on TRAF6, leading to activation of the nuclear factor- B (NF- B) pathway. Consistently, the effect of PDIA3P1 inhibition in promoting Dox-triggered apoptosis was antagonized by silencing the inhibitor of B (I B or overexpressing TRAF6. Administration of BAY 11-7085, an NF- B inhibitor, attenuated PDIA3P1-induced resistance to Dox treatment in mouse xenografts. Moreover, up-regulation of PDIA3P1 was significantly correlated with elevation of TRAF6, phosphorylated p65, or NF- B downstream anti-apoptosis genes in human HCC tissues. These data indicate that enhanced PDIA3P1 expression may confer chemoresistance by acting as a microRNA (miRNA) sponge to increase TRAF6 expression and augment NF- B signaling. Subsequent investigations into the mechanisms of PDIA3P1 up-regulation revealed that human homologue of mRNA transport mutant 4 (hMTR4), which promotes RNA degradation, could bind to PDIA3P1, and this interaction was disrupted by Dox treatment. Overexpression of hMTR4 attenuated Dox-induced elevation of PDIA3P1, whereas silencing hMTR4 increased PDIA3P1 level, suggesting that Dox may up-regulate PDIA3P1 by abrogating the hMTR4-mediated PDIA3P1 degradation. |
Pubmed ID | 31509261 |
Year | 2019 |
Title | A Novel hMTR4-PDIA3P1-miR-125/124-TRAF6 Regulatory Axis and Its Function in NF-?? Signaling and Chemoresistance |
External Links
Links for PDIA3P1 | GenBank HGNC NONCODE |
Links for hepatocellular carcinoma | OMIM COSMIC |