Long noncoding RNA PART1 promotes progression of non‐small cell lung cancer cells via JAK‐STAT signaling pathway

Abstract

Non‐small cell lung cancer (NSCLC), the major type of lung cancer, becomes the greatest threat to the life of people. Growing evidence shows prostate androgen‐regulated transcript 1 (PART1) is considered as effective markers for prostate cancer, and has been shown to be associated with poor prognosis of NSCLC. However, the tumorigenic mechanism of PART1 in NSCLC remains to be investigated. In this study, we found that the expression of PART1 was robustly induced in NSCLC tissues and cell lines. Functional studies established that overexpression of PART1 could promote NSCLC cell proliferation, migration, and invasion, while interference of PART1 inhibited NSCLC progression. Our results also identified miR‐635 as a novel target of PART1, whose expression was inhibited by PART1 in NSCLC cell lines. Moreover, gain‐ and loss‐of‐function studies revealed that PART1 could sponge miR‐635 and increase the expression of Janus kinase (JAK) and signal transducer and activator of transcription proteins (STATs). Finally, we deciphered the molecular mechanism by which PART1 contributed to promotion of NSCLC cell progression via phosphorylation and activation of JAK‐STAT signaling pathway. The animal experiment further confirmed that interference of NSCLC could suppress in vivo tumorigenic ability of NSCLC with favorable pharmacological activity via inactivation of JAK‐STAT signaling pathway. In conclusion, our findings clarified the biologic significance of PART1/miR‐635/JAK‐STAT axis in NSCLC progression and provided novel evidence that PART1 may be a new potential therapeutic target for the treatment of NSCLC.

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

“…Sustained activation of JAK/STAT signaling has been demonstrated in tumor initiation, progression, and cancer stem cell (CSC) maintenance in several human cancers. For instance, Zhu et al (2019) reported that long non-coding RNA PART1 enhanced the proliferation, migration, and invasion via activation of JAK-STAT signaling in non-small-cell lung cancer cells. Dolatabadi et al (2019) demonstrated that the activation of JAK-STAT signaling regulates the CSC properties in myxoid liposarcoma.…”

lncRNA PART1 and MIR17HG as ΔNp63α direct targets regulate tumor progression of cervical squamous cell carcinoma

“…Among the 39 directly regulated lncRNAs, previous studies indicated that lncPART1 and lncMIR17HG are associated to tumorigenesis 42‐47 . Besides, lncPART1 and lncMIR17HG demonstrated significant differential expression in ME‐180/shp63 cells.…”

<p>Inhibition of lncRNA PART1 Chemosensitizes Wild Type but Not KRAS Mutant NSCLC Cells</p>

“…This indicated that lncRNA PART1 is overexpressed in NSCLC cell lines, corroborating previous studies. 22,23 We then investigated if modulating PART1 expression will alter chemosensitivity of BEAS-2B or the NSCLC cell lines. PART1 was overexpressed in BEAS-2B cells, whereas the NSCLC cells lines were transfected with PART1 siRNA.…”

“…21,25,26 PART1 has been indicated previously in glioblastoma, 27 esophageal squamous cell carcinoma (ESCC), 28 oral cancer, 29 colorectal cancer, 30 as well as in survival and disease progression of NSCLC. 22,23 However, there has been no previous study elucidating a role of PART1 in chemoresistance to erlotinib in NSCLC.…”

“…21 PART1 is also expressed in lungs of NSCLC patients and was found to be correlated to survival 22 as well as disease progression via JAK-STAT signaling pathway. 23 Given its apparent importance in pathogenesis of NSCLC, 20,23 our objective was to study if PART1 expression indirectly or directly regulates chemosensitivity of NSCLC cells. Interestingly, our results show that inhibition of PART1 sensitized NSCLC cell lines to erlotinib treatment whereas its overexpression in normal lung epithelial cells rendered them resistant to erlotinib treatment.…”