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

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.
Authors	Xiaoli Liu, Zuwei Yin, Linping Xu, Huaimin Liu, Lifeng Jiang, Shuochuan Liu, Xu Sun
Journal	Cell death & disease (Cell Death Dis) Vol. 12 Issue 2 Pg. 173 (02 10 2021) ISSN: 2041-4889 [Electronic] England
PMID	33568633 (Publication Type: Journal Article)
Chemical References	Hedgehog Proteins RNA, Long Noncoding SHH protein, human Ubiquitin Thiolesterase Usp22 protein, human
Topics	A549 Cells Adenocarcinoma of Lung (genetics, metabolism, pathology) Animals Apoptosis Cell Movement Cell Proliferation Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic Hedgehog Proteins (genetics, metabolism) Humans Lung Neoplasms (genetics, metabolism, pathology) Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Neoplastic Stem Cells (metabolism, pathology) Phenotype Proteolysis RNA, Long Noncoding (genetics, metabolism) Signal Transduction Ubiquitin Thiolesterase (metabolism) Ubiquitination Up-Regulation Mice

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