LncRNA HOTAIR promotes the growth and metastasis of gastric cancer by sponging miR-1277-5p and upregulating COL5A1.
COL5A1
Gastric cancer
HOTAIR
Immune infiltration
MiR-1277-5p
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
03
02
2020
accepted:
21
05
2020
pubmed:
26
6
2020
medline:
5
8
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown. HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas. We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1-mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC. HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.
Sections du résumé
BACKGROUND
Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown.
METHODS
HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas.
RESULTS
We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1-mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC.
CONCLUSIONS
HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.
Identifiants
pubmed: 32583079
doi: 10.1007/s10120-020-01091-3
pii: 10.1007/s10120-020-01091-3
doi:
Substances chimiques
COL5A1 protein, human
0
Collagen Type V
0
HOTAIR long untranslated RNA, human
0
MIRN1277 microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1018-1032Subventions
Organisme : Natural Science Project of Anhui Province
ID : KJ2017A829
Pays : International
Références
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
pubmed: 30207593
Best LMJ, Mughal M, Gurusamy KS. Laparoscopic versus open gastrectomy for gastric cancer. Cochrane DB Syst Rev. 2016;3:CD011389.
Wagner AD, Syn NLX, Moehler M, Grothe W, Yong WP, Tai B-C, et al. Chemotherapy for advanced gastric cancer. Cochrane DB Syst Rev. 2017;8:CD004064.
Rebekka Schirren DRaARN. Adjuvant and/or neoadjuvant therapy for gastric cancer? A perspective review. Ther Adv Med Oncol. 2015;7:39–48.
Gomez-Martín C, Lopez-Rios F, Aparicio J, Barriuso J, García-Carbonero R, Pazo R, et al. A critical review of HER2-positive gastric cancer evaluation and treatment: from trastuzumab, and beyond. Cancer Lett. 2014;351:30–40.
pubmed: 24943493
Novikova IV, Hennelly SP, Tung C-S, Sanbonmatsu KY. Rise of the RNA machines: exploring the structure of long non-coding RNAs. J Mol Biol. 2013;425:3731–46.
pubmed: 23467124
Mohammadreza Hajjari AS. HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med. 2015;12:1–9.
pubmed: 25859406
pmcid: 4383848
Liu XHSM, Nie FQ, Ge YB, Zhang EB, Yin DD, Kong R, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.
pubmed: 24775712
pmcid: 4021402
Wang HQR, Guan A, Yao Y, Huang Y, Jia H, Huang W, et al. HOTAIR enhanced paclitaxel and doxorubicin resistance in gastric cancer cells partly through inhibiting miR-217 expression. J Cell Biochem. 2018;119:7226–344.
pubmed: 29856087
Lu P, Weaver VM, Werb Z. The extracellular matrix: A dynamic niche in cancer progression. J Cell Biol. 2012;196:395–406.
pubmed: 22351925
pmcid: 3283993
Kauppila SSF, Risteli J, Jukkola A, Risteli L. Aberrant type I and type III collagen gene expression in human breast cancer in vivo. J Pathol. 1998;186:262–8.
pubmed: 10211114
Wozniak MA, Desai R, Solski PA, Der CJ, Keely PJ. ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J Cell Biol. 2003;163:583–95.
pubmed: 14610060
pmcid: 2173660
Kaplan G. In vitro differentiation of human monocytes. Monocytes cultured on glass are cytotoxic to tumor cells but monocytes cultured on collagen are not. J Exp Med. 1983;157:2061–72.
pubmed: 6682883
Liu W, Wei H, Gao Z, Chen G, Liu Y, Gao X, et al. COL5A1 may contribute the metastasis of lung adenocarcinoma. Gene. 2018;665:57–66.
pubmed: 29702185
Zhang JJ, Yano H, Sasaki T, Matsuo N, Yoshioka H. The pro-alpha1(V) collagen gene (Col5a1) is coordinately regulated by miR-29b with core promoter in cultured cells. Connect Tissue Res. 2018;59:263–73.
pubmed: 28829698
Zhao X, Cai H, Wang X, Ma L. Discovery of signature genes in gastric cancer associated with prognosis. Neoplasma. 2016;63:239–45.
pubmed: 26774142
Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42:D92–97.
pubmed: 24297251
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98–W102.
pubmed: 28407145
pmcid: 5570223
LA Szász AM, Nagy Á, Förster S, Hark K, Green JE, Boussioutas A, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1065 patients. Oncotarget. 2016;7:49322–33.
pubmed: 27384994
pmcid: 5226511
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607–D613613.
pubmed: 30476243
Yoshihara KSM, Martínez E, Vegesna R, Kim H, Torres-Garcia W, Treviño V, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.
pubmed: 24113773
Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, et al. TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017;77:e108–e110110.
pubmed: 29092952
pmcid: 6042652
Alatengbaolide LD, Li Y, Xu H, Chen J, Wang B, et al. Lymph node ratio is an independent prognostic factor in gastric cancer after curative resection (R0) regardless of the examined number of Lymph Nodes. Am J Clin Oncol. 2013;36:325–30.
pubmed: 22547011
Bilici A, Selcukbiricik F, Seker M, Oven BB, Olmez OF, Yildiz O, et al. Prognostic significance of metastatic lymph node ratio in patients with pn3 gastric cancer who underwent curative gastrectomy. Oncol Res Treat. 2019;42:209–16.
pubmed: 30870846
Lin CL, Zhu GW, Huang YJ, Zheng W, Yang SG, Ye JX. Operable gastric adenocarcinoma with different histological subtypes: Cancer-specific survival in the United States. Saudi J Gastroenterol. 2020;26:46–52.
pubmed: 32031158
Li Z, Cen H. Construction of a nomogram for the prediction of prognosis in patients with resectable gastric cancer undergoing fewer than sixteen lymph node biopsies. Onco Targets Ther. 2019;12:7415–28.
pubmed: 31686848
pmcid: 6752044
Komatsu S, Ichikawa D, Nishimura M, Kosuga T, Okamoto K, Konishi H, et al. Evaluation of prognostic value and stage migration effect using positive lymph node ratio in gastric cancer. Eur J Surg Oncol. 2017;43:203–9.
pubmed: 27595506
Kim Y, Squires MH, Poultsides GA, Fields RC, Weber SM, Votanopoulos KI, et al. Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy. Surgery. 2017;162:285–94.
pubmed: 28578142
Yamashita K, Hosoda K, Ema A, Watanabe M. Lymph node ratio as a novel and simple prognostic factor in advanced gastric cancer. Eur J Surg Oncol. 2016;42:1253–60.
pubmed: 27017273
Guo D, Li Y, Chen Y, Zhang D, Wang X, Lu G, et al. DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway. Cell Prolif. 2019;52:e12628.
pubmed: 31038266
pmcid: 6668976
Zhou X, Chen J, Tang W. The molecular mechanism of HOTAIR in tumorigenesis, metastasis, and drug resistance. Acta Bioch Bioph Sin. 2014;46:1011–5.
Wanmin Song KJ, McGuire PG. Degradation of type IV collagen by matrix metalloproteinases is an important step in the epithelial-mesenchymal transformation of the endocardial cushions. Dev Biol. 2000;227:606–17.
Radisky ES, Radisky DC. Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J Mammary Gland Biol. 2010;15:201–12.
Armstrong TPG, Murphy LB, Bateman AC, Conti JA, Fine DR, Johnson CD, et al. Type I collagen promotes the malignant phenotype of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2004;10:7427–37.
pubmed: 15534120
Sok JC, Lee JA, Dasari S, Joyce S, Contrucci SC, Egloff AM, et al. Collagen type XI alpha1 facilitates head and neck squamous cell cancer growth and invasion. Br J Cancer. 2013;109:3049–56.
pubmed: 24231953
pmcid: 3859935
Vazquez-Villa F, Garcia-Ocana M, Galvan JA, Garcia-Martinez J, Garcia-Pravia C, Menendez-Rodriguez P, et al. COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression. Tumor Biol. 2015;36:2213–22.
Feng G, Ma HM, Huang HB, Li YW, Zhang P, Huang JJ, et al. Overexpression of COL5A1 promotes tumor progression and metastasis and correlates with poor survival of patients with clear cell renal cell carcinoma. Cancer Manag Res. 2019;11:1263–74.
pubmed: 30799953
pmcid: 6369854
Ren W, Zhang Y, Zhang L, Lin Q, Zhang J, Xu G. Overexpression of collagen type V alpha1 chain in human breast invasive ductal carcinoma is mediated by TGF-beta1. Int J Oncol. 2018;52:1694–704.
pubmed: 29568948
Hamy AS, Bonsang-Kitzis H, De Croze D, Laas E, Darrigues L, Topciu L, et al. Interaction between molecular subtypes and stromal immune infiltration before and after treatment in breast cancer patients treated with neoadjuvant chemotherapy. Clin Cancer Res. 2019;25:6731–41.
pubmed: 31515462
Sokratous G, Polyzoidis S, Ashkan K. Immune infiltration of tumor microenvironment following immunotherapy for glioblastoma multiforme. Hum Vacc Immunother. 2017;13:2575–82.
Mao Y, Feng Q, Zheng P, Yang L, Liu T, Xu Y, et al. Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer. Cancer Manag Res. 2018;10:3569–77.
pubmed: 30271205
pmcid: 6149864
Aran DSM, Butte AJ. Systematic pan-cancer analysis of tumour purity. Nat Commun. 2015;6:8971.
pubmed: 26634437