JAK2 overexpression

Mechanistically, activation of the JAK/STAT3 pathway by JAK1 or JAK2 overexpression attenuated VAMP8 silencing-mediated anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on CRC cells. In conclusion, VAMP8 knockdown affects the proliferation, apoptosis, autophagy, and ferroptosis by the JAK/STAT3 pathway in CRC cells.

In contrast, ruxolitinib, a well-known inhibitor of JAK2V617F, clearly blocked GRP78 expression in these cells through downregulation of transcription factor 4 (ATF4)...An anti-GRP78 neutralizing antibody abrogated LOX elevation; in contrast, recombinant GRP78 protein induced LOX protein expression in HS-5 cells. Our observations suggest that the oncogenic protein JAK2V617F induces overexpression and release of GRP78, which may induce a fibrotic phenotype in surrounding bone marrow stromal cells.

To address the mechanism responsible for the induction of GRP78, we treated the HEL and SET-2 cells with 4-phenyl butyric acid and tauroursodeoxycholic acid both of which are well known inhibitors of ER stress, however, these inhibitors did not affect the expression levels of GRP78...In contrast, ruxolitinib, an inhibitor of JAK2V617F, blocked GRP78 expression in these cells...In conclusion, we demonstrated that GRP78 was overexpressed both in MPN derived cell lines and also in primary megakaryocytes from MF patients. Our observations proposed that overexpressed GRP78 in MPN cells contribute development of myelofibrosis through secreted in microenvironment and induced expression of extracellular matrix modulating enzyme LOX in bone marrow stromal cells.

Our findings revealed that PsA may exert its antitumor effect by causing G1 arrest and apoptosis in DLBCL cells. The mechanism of PsA regulating apoptosis in DLBCL cells is probably through the JAK2/STAT3 signaling pathway in vitro.

Western blotting showed that MTP inhibited Janus kinase 2 (JAK2) signaling, and JAK2 overexpression partially reversed MTP-mediated cytotoxicity. Taken together, these data indicate the potential use of MTP as a therapeutic agent for OSCC.

In the FREEDOM study, FEDR treatment resulted in cytokine changes, some of which suggest an anti-inflammatory and anti-fibrotic effect. Changes to cytokine profile, specifically anti-inflammatory effects, are a potential disease-modifying effect in MF therapies. Preclinical studies at clinically relevant exposures further demonstrated that FEDR inhibited proliferation and STAT phosphorylation in RUX-resistant cell lines, and had a broader kinase inhibition profile compared with RUX.

In addition, the in vivo results further confirmed that oridonin inhibited tumorigenicity in thyroid cancer xenograft. In conclusion, the results demonstrated that oridonin repressed metastatic phenotype, angiogenesis and modulated EMT (epithelial-mesenchymal transition) of thyroid cancer cells via the inactivation of JAK2/STAT3 signaling pathway, suggesting that JAK2 may be a novel therapeutic target of oridonin against thyroid cancer.

KEGG and GO analysis demonstrated that these genes were mainly implicated in cytokine response, cell proliferation, differentiation, and leukemia evolution illustrating that the development of MPN and its possible risk of transformation in this mouse model is largely TP53 independent. Conclusion Taken together, our results show that a large part of genetic modifications induced by JAK2V617F mutation are p53 dependent but MPN phenotype is not, TP53 loss is insufficient to induce quick leukemic transformation in steady-state hematopoiesis in Jak2 V617F MPN despite it increases LT-HSC cell proliferation and finally that TP53 loss could be involved in IFN resistance in MPN.

CRLF2 expression was significantly higher in Egyptian precursor B-ALL pediatric patients. CRLF2 overexpression was associated with a number of unfavorable prognostic factors with high tumor load, but was not an adverse independent parameter in pediatric BCP-ALL patients. Some patients with CRLF2 overexpression display JAK2 mutation, which may benefit from targeted therapy by kinase inhibitors.

In conclusion, Cbl alleviates endothelial dysfunction by inactivation of the JAK2/STAT4 pathway and inhibition of Runx3 expression in DM. These evidence might underlie novel Cbl-based treatment against DM in the future.

MIAT knockdown inhibited apoptosis and inflammation by regulating JAK2/STAT3 signaling pathway via targeting miR-181a-5p in myocardial ischemia model. MIAT can be a possible therapeutic target for controlling the progression of myocardial ischemia.

Immunohistochemistry showed that most extramammary Paget's disease tissues were positive for Janus kinase 2 (50/53, 94.3%), and the immunostaining intensity of Janus kinase 2 was correlated with the degree of invasiveness, lymph node metastasis and distant metastasis. Based on these findings, Janus kinase 2 may be a promising therapeutic target in extramammary Paget's disease.

MUC16 contributes to the development and progression of CRC by binding to JAK2, thereby promoting phosphorylation of JAK2 and further activating STAT3 phosphorylation.

This study reveals that silence of LOC100132707 represses the migration of UM via downregulating JAK2. The LOC100132707/JAK2 axis might serve as a potent target for the prevention and treatment of UM metastasis.

Pathologically, EBVaGC is a gastric adenocarcinoma with lymphoid stroma. This review interprets how the EBV genome is involved in the oncogenesis of gastric cancer and describes the molecular and clinicopathological features of EBVaGC.

TTTY15 could indirectly modulate JAK2, and overexpression of TTTY15 could reverse the inhibitory effects of miR-337-3p on malignant phenotypes of ESCC cells. In conclusion, TTTY15 plays an oncogenic role in ESCC by targeting miR-337-3p/JAK2 axis.

Taken together, it is indicated in our research that ZNF667-AS1 interaction with ANK2/JAK2 maybe important in CRC progression. Overexpression of ZNF667-AS1 could inhibit the proliferation, migration, and invasion of CRC cells, which may be related with the high ANK2 and low JAK2 levels.