Open AccessLong noncoding RNA PART1 promotes progression of non‐small cell lung cancer cells via JAK‐STAT signaling pathway
Author(s) -
Zhu Dengyan,
Yu Yang,
Wang Wei,
Wu Kai,
Liu Donglei,
Yang Yang,
Zhang Chunyang,
Qi Yu,
Zhao Song
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2494
Subject(s) - cancer research , stat protein , janus kinase , jak stat signaling pathway , rna interference , biology , stat , lung cancer , signal transduction , stat3 , cell growth , prostate cancer , cancer , medicine , rna , microbiology and biotechnology , gene , tyrosine kinase , genetics
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.