JAK2 variations and functions in lung adenocarcinoma

Abstract

Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains low. JAK2 has emerged as pivotal participant in biological processes, often dysregulated in a range of cancers. Recently our study found that JAK2 might play an important role in lung cancer pathogenesis. While our understanding of JAK2 in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the variations and functions of JAK2 will certainly secure strong biomarkers and improve treatment options for lung cancer patients. The expression level of JAK2 mRNA was assayed using RT-PCR. JAK2 mutations and amplification were detected using next-generation sequencing (NGS). The shRNA and overexpression plasmids of JAK2 were conducted. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazoliumbromide) assay, Trans-well migration and Matrigel invasion assay were conducted to study the proliferation, migration and invasion abilities of lung adenocarcinoma cells independently. We found that JAK2 mRNA was up-regulated in lung adenocarcinoma tissues when compared with their adjacent non-tumor tissues, and was associated with lymph node metastasis ( p < 0.05). JAK2 V617F and N30S mutations and JAK2 amplification were detected by NGS in plasmid samples in patients with lung adenocarcinoma. Downregulation of JAK2 inhibited the proliferation, migration and invasion abilities of lung adenocarcinoma A549 cells. Moreover, overexpression of JAK2 induced the proliferation, migration and invasion abilities of A549 cells. Thus, the up-regulation, mutation and amplification of JAK2 detected in lung adenocarcinoma may participate in lung cancer progression by regulating cancer cells' proliferation, migration and invasion.

PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

“…The JAK/STAT signaling pathway is a downstream pathway of cytokine signaling, which regulates cell differentiation, proliferation, and apoptosis and plays an important role in the occurrence and development of tumors 33 . Compared with adjacent nontumor tissues, JAK2 mRNA expression was upregulated in LUAD tissues, and overexpression of JAK2 induced A549 cell proliferation, migration, and invasion capabilities 34 . Xu and Lu 35 demonstrated that high expression of STAT3 or p‐STAT3 is a powerful predictor of poor prognosis in patients with NSCLC.…”

“…33 Compared with adjacent nontumor tissues, JAK2 mRNA expression was upregulated in LUAD tissues, and overexpression of JAK2 induced A549 cell proliferation, migration, and invasion capabilities. 34 Xu and Lu 35 demonstrated that high expression of STAT3 or p-STAT3 is a powerful predictor of poor prognosis in patients with NSCLC. In our study, PYCR1 knockdown was found to inhibit the proliferation and migration of LUAD cells, while increasing the expression of JAK2, STAT3, and p-STAT3.…”

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

“…For instance, JAK2 is frequently mutated in myeloproliferative disorders . Dysregulated JAK2 influences the proliferation and aggression of lung adenocarcinoma cells . To our best knowledge, dysregulation of JAK2 in several cancer types, such as colorectal cancer, gastric cancer and thyroid cancer, is mainly caused by the up‐ or downregulation of upstream miR‐375 .…”

“…25 Dysregulated JAK2 influences the proliferation and aggression of lung adenocarcinoma cells. 26 To our best knowledge, dysregulation of JAK2 in several cancer types, such as colorectal cancer, gastric cancer and thyroid cancer, is mainly caused by the up-or downregulation of upstream miR-375. [27][28][29] However, whether the JAK2 expression in HCC is also mediated by miR-375 remains unknown.…”

Molecular analysis of V617F mutation in Janus kinase 2 gene of breast cancer patients

“…Involvement of JAK2 in myeloproliferative neoplasms is well-established (Bader and Dreiling, 2019, Mata et al, 2007, Panani, 2009, Xu et al, 2014). It is also associated with other malignancies like leukaemia (Singh et al, 2018) and cancers of skin (Pritchard et al, 2018), lung (Li et al, 2017, Xu et al, 2017), and stomach (Judd et al, 2014).…”