Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression

Abstract

Our previous studies demonstrated that Jab1/Csn5 overexpression is correlated with low survival rates in cancer patients including nasopharyngeal carcinoma (NPC), breast cancer, hepatocellular carcinoma, and contributes to NPC’s resistance to radiotherapy and cisplatin by regulating DNA damage and repair pathways. However, the molecular mechanism by which Jab1/Csn5 expression is upregulated in NPCs has yet to be determined. In the present study, we identified the upstream regulator of Jab1/Csn5 expression and demonstrated its role in intrinsic resistance of NPC cells to treatment with cisplatin. Signal transducer and activator of transcription-3 (Stat3) expression correlates with and contributes to Jab1/Csn5 transcription. Consistently, silencing of Stat3 in tumors reduced Jab1/Csn5 expression, thereby sensitizing NPC cells to cisplatin-induced apoptosis both in vitro and in vivo. Mechanistically, Stat3 transcriptionally regulated Jab1/Csn5. Further, high mRNA expression levels of Stat3 or Jab1 in colon cancer, breast cancer, and glioblastoma are associated with significantly shorter survival times from the R2 online database. These findings identify a novel Stat3-Jab1/Csn5 signaling axis in cancer pathogenesis with therapeutic and prognostic relevance.

α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

“…α5‐nAChR modulates lung tumour cells invasion and migration, promoting tumour metastasis . P‐Stat3 regulates the progression of nasopharyngeal and breast cancer by activating Jab1 . JAK/Stat3 and Jab1 are implicated in the mechanisms of EMT in different types of human cancer.…”

“…20 Increasing evidence indicates that Jab1 activity mediates various tumorigenesis-associated pathways 21 and is a potential target for smoking-induced lung cancer. 22 P-Stat3 regulates the progression of nasopharyngeal and breast cancer by activating Jab1, 23,24 which regulates the expression of ZEB1 and affects the EMT process in renal cancer cells (RCCs). 25 Notably, the down-regulation of Jab1 decreases PD-L1 expression in cancer cells and sensitizes them to anti-CTLA4 therapy.…”

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

“…A cell invasion assay was performed using a BD BioCoat Matrigel invasion chamber (Franklin Lakes, NJ) as previously described [26]. Breast cancer cells were incubated in the upper chamber at a density of 2000 cells/well.…”

“…For IHC staining on TMA, 4 μm thick paraffin-embedded tissue sections were mounted on slides. The IHC procedure was conducted as described in our previous work [26].…”

Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference

“…Notably, in contrast to a previously described "odd-even" effect on DNA and mRNA delivery (18,21), we unveiled different rules associated with these unique features that govern the coassembly and resulting gene-silencing efficiency of siRNA/Ago2 complexes through biophysical and polymer chemistry approaches. Finally, to demonstrate the therapeutic potential of our system, as a proof-of-concept we chose to target signal transducer and activator of transcription 3 (STAT3), whose overexpression has been linked to tumor progression, drug resistance, promotion of cancer stem cells, and immune evasion in different cancers (22)(23)(24). To this end, we explored whether codelivering anti-STAT3 siRNA with Ago2 Fig.…”