Knockdown of long non-coding RNA linc-ITGB1 inhibits cancer stemness and epithelial-mesenchymal transition by reducing the expression of Snail in non-small cell lung cancer.
Animals
Apoptosis
Carcinoma, Non-Small-Cell Lung
/ genetics
Cell Proliferation
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ genetics
Mice
Mice, Inbred BALB C
Mice, Nude
RNA, Long Noncoding
/ genetics
Snail Family Transcription Factors
/ genetics
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Cancer stem cell
epithelial-mesenchymal transition
linc-ITGB1
non-small cell lung cancer
snail
Journal
Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
19
09
2018
revised:
10
10
2018
accepted:
10
10
2018
pubmed:
30
11
2018
medline:
8
2
2020
entrez:
29
11
2018
Statut:
ppublish
Résumé
The main cause of death in patients with non-small cell lung cancer (NSCLC) is the progression of cancer metastasis, which can be attributed to multiple factors, such as cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) play important roles in the regulation of the cell cycle, cell proliferation, immune responses, and metastasis in cancers, but the potential roles and mechanisms of lincRNAs in CSC-like properties of cancer have not yet been elucidated. Human NSCLC cell lines (A549 and H1299), highly metastatic cell lines (L9981 and 95D), and their corresponding low-metastatic cell lines (NL9980 and 95C) were subject to quantitative real-time PCR and Western blot, transwell invasion, colony formation, and wound healing assays. Linc-ITGB1 was greatly upregulated in CSC spheres. Linc-ITGB1 knockdown markedly inhibited CSC formation and the expression of stemness-associated genes, such as Sox2, Nanog, Oct-4, c-Myc, and CD133. Depletion of linc-ITGB1 expression also inhibited the in vitro invasive and migratory potential of cells, and further analysis indicated that linc-ITGB1 knockdown increased the expression of the epithelial marker E-cadherin and downregulated the mesenchymal markers vimentin and fibronectin. The EMT-related transcription factor Snail mediated these effects of linc-ITGB1 in NSCLC, and overexpression of Snail significantly reversed the inhibitory effects of linc-ITGB1 depletion. Overall, our study demonstrated that linc-ITGB1 promoted NSCLC cell EMT and cancer stemness by regulating Snail expression.
Sections du résumé
BACKGROUND
The main cause of death in patients with non-small cell lung cancer (NSCLC) is the progression of cancer metastasis, which can be attributed to multiple factors, such as cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) play important roles in the regulation of the cell cycle, cell proliferation, immune responses, and metastasis in cancers, but the potential roles and mechanisms of lincRNAs in CSC-like properties of cancer have not yet been elucidated.
METHODS
Human NSCLC cell lines (A549 and H1299), highly metastatic cell lines (L9981 and 95D), and their corresponding low-metastatic cell lines (NL9980 and 95C) were subject to quantitative real-time PCR and Western blot, transwell invasion, colony formation, and wound healing assays.
RESULTS
Linc-ITGB1 was greatly upregulated in CSC spheres. Linc-ITGB1 knockdown markedly inhibited CSC formation and the expression of stemness-associated genes, such as Sox2, Nanog, Oct-4, c-Myc, and CD133. Depletion of linc-ITGB1 expression also inhibited the in vitro invasive and migratory potential of cells, and further analysis indicated that linc-ITGB1 knockdown increased the expression of the epithelial marker E-cadherin and downregulated the mesenchymal markers vimentin and fibronectin. The EMT-related transcription factor Snail mediated these effects of linc-ITGB1 in NSCLC, and overexpression of Snail significantly reversed the inhibitory effects of linc-ITGB1 depletion.
CONCLUSION
Overall, our study demonstrated that linc-ITGB1 promoted NSCLC cell EMT and cancer stemness by regulating Snail expression.
Identifiants
pubmed: 30485693
doi: 10.1111/1759-7714.12911
pmc: PMC6360263
doi:
Substances chimiques
RNA, Long Noncoding
0
SNAI1 protein, human
0
Snail Family Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
128-136Informations de copyright
© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Références
Endocrine. 2016 Jul;53(1):145-56
pubmed: 26370117
Mol Biosyst. 2012 Sep;8(9):2289-94
pubmed: 22722759
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
pubmed: 12629218
Mol Cell. 2014 Jun 5;54(5):716-27
pubmed: 24905005
Cell Death Differ. 2017 May;24(5):785-797
pubmed: 28186499
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
pubmed: 24556840
Cancer Res. 2017 Aug 1;77(15):3965-3981
pubmed: 28701486
Exp Hematol Oncol. 2016 Dec 12;5:30
pubmed: 27999732
Nat Med. 2013 Nov;19(11):1438-49
pubmed: 24202396
Chem Biol Drug Des. 2015 Nov;86(5):1064-71
pubmed: 25893892
Cell. 2016 Jun 30;166(1):21-45
pubmed: 27368099
Mol Oncol. 2017 Jan;11(1):28-39
pubmed: 28085222
Mol Cancer. 2011 Apr 13;10:38
pubmed: 21489289
Cell. 2008 May 16;133(4):704-15
pubmed: 18485877
Biotechnol Appl Biochem. 2017 Jan;64(1):5-13
pubmed: 26601916
Cancer Lett. 2018 May 1;421:121-126
pubmed: 29331418
Adv Exp Med Biol. 2016;927:137-72
pubmed: 27376734
Biochim Biophys Acta. 2013 Oct;1832(10):1528-37
pubmed: 23688781
Semin Cancer Biol. 2012 Oct;22(5-6):396-403
pubmed: 22554795
Nature. 2015 Nov 26;527(7579):525-530
pubmed: 26560028
Exp Ther Med. 2017 Nov;14(5):4687-4692
pubmed: 29201168
Cancer Lett. 2013 Jun 10;333(2):213-21
pubmed: 23354591
Nature. 2010 Apr 15;464(7291):1071-6
pubmed: 20393566