Loss of MIR503HG facilitates papillary renal cell carcinoma associated lymphatic metastasis by triggering NOTCH1/VEGFC signaling.
DNA methylation
Long non-coding RNA
Lymphatic metastasis
Papillary renal cell carcinoma
Target therapy
Journal
International journal of biological sciences
ISSN: 1449-2288
Titre abrégé: Int J Biol Sci
Pays: Australia
ID NLM: 101235568
Informations de publication
Date de publication:
2023
2023
Historique:
received:
07
02
2023
accepted:
02
06
2023
medline:
10
7
2023
pubmed:
7
7
2023
entrez:
7
7
2023
Statut:
epublish
Résumé
Clinical lymphatic metastasis indicates an extremely poor prognosis. Patients with papillary renal cell carcinoma (pRCC) have a high probability of progressing to lymphatic metastasis. However, the molecular mechanism of pRCC-associated lymphatic metastasis has not been elucidated. In this study, we found a downregulated long non-coding RNA (lncRNA) MIR503HG in pRCC primary tumor tissues due to hypermethylation at the CpG islands within its transcriptional start site. Decreased MIR503HG expression could stimulate tube formation and migration of human lymphatic endothelial cell (HLEC) and play a central role to promote lymphatic metastasis in vivo by enhancing tumor lymphangiogenesis. MIR503HG, located in the nucleus, bound with histone variant H2A.Z and affected the recruitment of histone variant H2A.Z to chromatin. Subsequently, increasing the H3K27 trimethylation caused by MIR503HG-overexpression epigenetically downregulated the NOTCH1 expression, which ultimately resulted in decreasing VEGFC secretion and lymphangiogenesis. Additionally, downregulated MIR503HG facilitated the HNRNPC expression, which ultimately promoted the maturation of NOTCH1 mRNA. Notably, upregulating MIR503HG expression might decrease pRCC resistance to the mTOR inhibitor. Together, these findings highlighted a VEGFC-independent mechanism of MIR503HG-mediated lymphatic metastasis. MIR503HG, identified as a novel pRCC-suppressor, would serve as the potentially biomarker for lymphatic metastasis.
Identifiants
pubmed: 37416763
doi: 10.7150/ijbs.83302
pii: ijbsv19p3266
pmc: PMC10321273
doi:
Substances chimiques
Histones
0
NOTCH1 protein, human
0
Receptor, Notch1
0
RNA, Long Noncoding
0
long non-coding RNA MIR503HG, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3266-3284Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
Références
Cancer Res. 2011 Nov 15;71(22):7103-12
pubmed: 21975930
BMC Biol. 2018 Sep 24;16(1):107
pubmed: 30249243
Cancer Cell. 2014 Sep 8;26(3):319-330
pubmed: 25155756
J Hepatol. 2019 May;70(5):918-929
pubmed: 30582981
Nat Commun. 2015 Feb 18;6:6370
pubmed: 25691256
J Clin Oncol. 2005 Apr 20;23(12):2763-71
pubmed: 15837991
Cell Death Dis. 2022 Aug 13;13(8):703
pubmed: 35963855
Eur J Cancer. 2016 Dec;69:226-235
pubmed: 27680407
Theranostics. 2018 Apr 15;8(10):2814-2829
pubmed: 29774077
Eur Urol. 2008 Mar;53(3):571-8
pubmed: 17804149
J Clin Invest. 2014 Mar;124(3):922-8
pubmed: 24590277
Cancer Res. 2016 Jun 15;76(12):3593-603
pubmed: 27197169
J Cell Mol Med. 2019 Jul;23(7):4738-4745
pubmed: 31062436
Cancer Lett. 2021 Oct 10;518:169-179
pubmed: 34273467
JAMA Netw Open. 2021 Jan 4;4(1):e2021869
pubmed: 33475752
Mol Cell. 2010 Jun 11;38(5):662-74
pubmed: 20541999
Gastroenterology. 2015 Jun;148(7):1438-51.e8
pubmed: 25754161
Clin Cancer Res. 2013 Jul 15;19(14):3719-21
pubmed: 23741068
Cancer Cell. 2020 Mar 16;37(3):270-288
pubmed: 32183948
Nucleic Acids Res. 2019 Aug 22;47(14):7580-7591
pubmed: 31147722
Cancer Res. 2017 Mar 1;77(5):1212-1226
pubmed: 28087600
Am J Surg Pathol. 2013 Oct;37(10):1469-89
pubmed: 24025519
N Engl J Med. 2016 Jan 14;374(2):135-45
pubmed: 26536169
Cell. 2013 Sep 26;155(1):107-20
pubmed: 24074864
Eur Urol. 2021 Aug;80(2):162-170
pubmed: 33867192
Cancer Cell. 2018 Apr 9;33(4):706-720.e9
pubmed: 29622465
Mol Oncol. 2016 Nov;10(9):1473-1484
pubmed: 27590684
Science. 2015 Nov 20;350(6263):978-81
pubmed: 26516199
Int J Oncol. 2022 Jul;61(1):
pubmed: 35616137
Cancer Lett. 2021 Oct 10;518:196-206
pubmed: 34271104
Cell Death Differ. 2017 Sep;24(9):1502-1517
pubmed: 28644440
Biochem Biophys Res Commun. 2016 Apr 8;472(3):465-70
pubmed: 26827826
Genes Dev. 2017 Aug 15;31(16):1615-1634
pubmed: 28947496
Mol Cancer. 2022 Apr 9;21(1):97
pubmed: 35395767
Adv Sci (Weinh). 2021 Sep;8(18):e2100881
pubmed: 34319001
J Natl Cancer Inst. 2005 Jan 5;97(1):14-21
pubmed: 15632376
Lymphat Res Biol. 2007;5(2):105-13
pubmed: 17935478
Mol Ther. 2021 Oct 6;29(10):2979-2994
pubmed: 34058384
Biochem Biophys Res Commun. 2017 Aug 26;490(3):913-919
pubmed: 28655612
Science. 2014 Apr 25;344(6182):376-80
pubmed: 24763583
Mol Cell Biochem. 2010 Dec;345(1-2):77-89
pubmed: 20734221
Cell. 2010 Feb 19;140(4):460-76
pubmed: 20178740
Nature. 2011 Apr 7;472(7341):120-4
pubmed: 21423168
J Clin Invest. 2018 Feb 1;128(2):861-875
pubmed: 29355840
Genome Res. 2017 Jan;27(1):27-37
pubmed: 27927715
Cancer Lett. 2022 Jun 28;536:215660
pubmed: 35318116
Cell Death Dis. 2020 Mar 2;11(3):163
pubmed: 32123166
Nat Rev Urol. 2019 Nov;16(11):655-673
pubmed: 31602010
Clin Cancer Res. 2012 Jul 1;18(13):3532-40
pubmed: 22753663
Cell Death Dis. 2021 Jun 12;12(6):609
pubmed: 34120148
J Cell Physiol. 2019 Jun;234(6):7948-7956
pubmed: 30644095
Mol Cancer. 2019 Dec 4;18(1):176
pubmed: 31801551
Nucleus. 2014 Jan-Feb;5(1):21-7
pubmed: 24637397
BJU Int. 2011 Jun;107(12):1930-5
pubmed: 20883486
Mol Cancer. 2016 Dec 19;15(1):83
pubmed: 27993170
Cancer Manag Res. 2020 Mar 05;12:1641-1647
pubmed: 32184667
J Cell Biochem. 2019 Jun;120(6):10821-10829
pubmed: 30672010
Cell Oncol (Dordr). 2021 Feb;44(1):219-233
pubmed: 33001357
Mol Cancer. 2020 Feb 10;19(1):28
pubmed: 32039732
N Engl J Med. 2017 Jan 26;376(4):354-366
pubmed: 28121507
Cell Oncol (Dordr). 2020 Oct;43(5):863-876
pubmed: 32729021
Nat Genet. 2015 Mar;47(3):199-208
pubmed: 25599403
Cancer Res. 2008 Oct 1;68(19):7828-37
pubmed: 18829538
Biomed Pharmacother. 2023 Apr;160:114314
pubmed: 36736276
J Clin Invest. 2020 Jan 2;130(1):404-421
pubmed: 31593555
Epigenetics Chromatin. 2019 Jun 13;12(1):35
pubmed: 31196171
Urol Oncol. 2018 Jun;36(6):311.e27-311.e35
pubmed: 29544697
Cancer Res. 2019 May 15;79(10):2536-2548
pubmed: 30940658
Oncogene. 2016 Sep 15;35(37):4866-80
pubmed: 26973243
Gene. 2019 Sep 10;713:143960
pubmed: 31278965
Essays Biochem. 2019 Apr 23;63(1):59-74
pubmed: 31015383