Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

Xiaoli Liu,Linping Xu,Zuwei Yin,Shuochuan Liu,Xu Sun,Huaimin Liu,Lifeng Jiang

doi:10.1038/s41419-021-03435-y

Abstract

Long noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

Highlights

Lung adenocarcinoma (LUAD) is a subtype of nonsmall cell lung cancer (NSCLC), which has become the most common cancer of tumor-related deaths all over the world[1,2,3]
The results indicated that the number of colonies reduced by LINC01426 silencing was apparently increased by the treatment SAG activator (Fig. 4A), indicating that LINC01426 functioned in LUAD cells potentially through activating the hedgehog pathway
Mounting evidence has revealed that Long noncoding RNAs (lncRNAs) play vital roles in the progression of LUAD

Summary

Introduction

Lung adenocarcinoma (LUAD) is a subtype of nonsmall cell lung cancer (NSCLC), which has become the most common cancer of tumor-related deaths all over the world[1,2,3]. Metastasis occurs in most of the LUAD patients at advanced stage[4]. Advances have been made in the diagnosis and therapy, the prognosis and overall survival of LUAD patients remain unoptimistic[5]. It is urgent to explore potential molecular mechanisms underlying LUAD progression to find novel therapeutic targets for LUAD patients. Long noncoding RNAs (lncRNAs) are characterized as a class of transcripts with lengths of more than 200 nucleotides and without protein-coding ability[6,7]. Accumulating evidence has indicated that lncRNAs are involved in the regulation of various cellular processes

Methods

Results

Conclusion