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

Yang Yang,Yang Yu,Chunyang Zhang,Dengyan Zhu,Kai Wu,Wei Wang,Yu Qi,Donglei Liu,Song Zhao

doi:10.1002/cam4.2494

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.

Highlights

Lung cancer, caused by a combination of genetic and environmental factors,[1] is the most common cause of cancer‐related mortality in human.[2]
Prostate androgen‐regulated transcript 1 (PART1) is a new long noncoding RNAs (lncRNAs) found in prostate tissues and cells via high‐throughput sequencing of RNA,[10] which is overexpressed in prostate cancer and is beneficial to the proliferation of prostate cancer cells through toll‐like signaling pathway.[11]
Recent studies have shown that various types of lncRNAs, such as TBILA,[26] NNT‐AS1,27,28 BLACAT1,29 exhibited biological functions and were involved in the progression of Non‐small cell lung cancer (NSCLC)

Summary

| INTRODUCTION

Lung cancer, caused by a combination of genetic and environmental factors,[1] is the most common cause of cancer‐related mortality in human.[2]. With the rapid development of molecular biology and gene diagnosis technology, more and more evidences show that long noncoding RNAs (lncRNAs), with 200 nucleotides in length, are closely related to the occurrence of cancer, and can be served as a specific tumor biomarker.[9] Prostate androgen‐regulated transcript 1 (PART1) is a new lncRNA found in prostate tissues and cells via high‐throughput sequencing of RNA,[10] which is overexpressed in prostate cancer and is beneficial to the proliferation of prostate cancer cells through toll‐like signaling pathway.[11] Otherwise, PART1 promotes tumor progression of colorectal cancer via sponging miR‐143 and regulating DNA‐methyltransferase 3A.12. The aim of this study was to detect whether lncRNA PART1 regulates progression of NSCLC via targeting JAK‐STAT signaling pathway through sponging of miR‐635

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION