LncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression.
Animals
Cell Line, Tumor
Cell Movement
/ genetics
Epigenesis, Genetic
Female
Gene Silencing
Humans
Liver Neoplasms
/ genetics
Lung Neoplasms
/ genetics
Lymphatic Metastasis
/ genetics
Male
Mice
Mice, Nude
Middle Aged
Neoplasm Staging
Proto-Oncogene Proteins c-akt
/ genetics
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
/ genetics
RNA, Long Noncoding
/ genetics
RNA, Small Interfering
STAT3 Transcription Factor
/ genetics
Sp1 Transcription Factor
/ genetics
Stomach Neoplasms
/ genetics
TOR Serine-Threonine Kinases
/ genetics
Up-Regulation
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
27 01 2020
27 01 2020
Historique:
received:
01
06
2019
accepted:
09
01
2020
revised:
07
01
2020
entrez:
29
1
2020
pubmed:
29
1
2020
medline:
2
10
2020
Statut:
epublish
Résumé
Gastric cancer (GC) is a highly prevalent type of metastatic tumor. The mechanisms underlying GC metastasis are poorly understood. Some long noncoding RNAs (lncRNAs) reportedly play key roles in regulating metastasis of GC. However, the biological roles of five natural antisense lncRNAs (AC093818.1, CTD-2541M15.1, BC047644, RP11-597M12.1, and RP11-40A13.1) in GC metastasis remain unclear. In this study, the expression of these lncRNAs was measured by quantitative reverse transcription-polymerase chain reaction. Migration and invasion were evaluated by wound-healing and the Transwell assay, respectively. Stable cells were injected into the tail veins of nude mice. Sections of collected lung and liver tissues were stained using hematoxylin and eosin. Protein expression was analyzed by western blot. RNA immunoprecipitation (RIP) assay was used to verify whether the STAT3 and SP1 transcription factors bound to AC093818.1 in GC cells. Expression levels of the five lncRNAs, especially AC093818.1, were significantly upregulated in metastatic GC tissues relative to those in nonmetastatic GC tissues. AC093818.1 expression was correlated with invasion, lymphatic metastasis, distal metastasis, and tumor-node-metastasis stage. AC093818.1 expression was highly sensitive and specific in the diagnosis of metastatic or nonmetastatic GC. AC093818.1 overexpression promoted GC migration and invasion in vitro and in vivo. AC093818.1 overexpression increased PDK1, p-AKT1, and p-mTOR expression levels. AC093818.1 silencing decreased these expressions. AC093818.1 bound to transcription factors STAT3 and SP1, and SP1 or STAT3 silencing could alleviated the effect of AC093818.1 overexpression. The data demonstrate that lncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression. LncRNA AC093818.1 may be a potential therapeutic target for metastatic GC.
Identifiants
pubmed: 31988283
doi: 10.1038/s41419-020-2245-2
pii: 10.1038/s41419-020-2245-2
pmc: PMC6985138
doi:
Substances chimiques
PDK1 protein, human
0
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
0
RNA, Long Noncoding
0
RNA, Small Interfering
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Sp1 Transcription Factor
0
SP1 protein, human
0
MTOR protein, human
EC 2.7.1.1
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
64Références
Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. https://doi.org/10.3322/caac.21492 (2018).
Torre, L. A. et al. Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87–108 (2015).
doi: 10.3322/caac.21262
Chen, W., Zheng, R., Zeng, H., Zhang, S. & He, J. Annual report on status of cancer in China, 2011. Chin. J. Cancer Res. 27, 2–12 (2015).
doi: 10.1186/s40880-015-0001-2
Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin. 68, 7–30 (2018).
doi: 10.3322/caac.21442
Liu, D. et al. The patterns and timing of recurrence after curative resection for gastric cancer in China. World J. Surg. Oncol. 14, 305 (2016).
doi: 10.1186/s12957-016-1042-y
Yamashita, K. et al. Trend in gastric cancer: 35 years of surgical experience in Japan. World J. Gastroenterol. 17, 3390–3397 (2011).
doi: 10.3748/wjg.v17.i29.3390
Yang, L., Froberg, J. E. & Lee, J. T. Long noncoding RNAs: fresh perspectives into the RNA world. Trends Biochem. Sci. 39, 35–43 (2014).
doi: 10.1016/j.tibs.2013.10.002
Kogo, R. et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 71, 6320–6326 (2011).
doi: 10.1158/0008-5472.CAN-11-1021
Khorkova, O., Hsiao, J. & Wahlestedt, C. Basic biology and therapeutic implications of lncRNA. Adv. Drug Deliv. Rev. 87, 15–24 (2015).
doi: 10.1016/j.addr.2015.05.012
Yin, D. D. et al. Decreased expression of long noncoding RNA MEG3 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Tumour Biol. 36, 4851–4859 (2015).
doi: 10.1007/s13277-015-3139-2
Renganathan, A. & Felley-Bosco, E. Long noncoding RNAs in cancer and therapeutic potential. Adv. Exp. Med. Biol. 1008, 199–222 (2017).
doi: 10.1007/978-981-10-5203-3_7
Wang, Y. et al. Long noncoding RNA Z38 promotes cell proliferation and metastasis and inhibits cell apoptosis in human gastric cancer. Oncol. Lett. 16, 6051–6058 (2018).
pubmed: 30333877
pmcid: 6176416
Luo, Y. et al. The long non-coding RNA LINC01606 contributes to the metastasis and invasion of human gastric cancer and is associated with Wnt/beta-catenin signaling. Int. J. Biochem. Cell Biol. 103, 125–134 (2018).
doi: 10.1016/j.biocel.2018.08.012
Lian, D., Amin, B., Du, D. & Yan, W. Enhanced expression of the long non-coding RNA SNHG16 contributes to gastric cancer progression and metastasis. Cancer Biomark.: Sect. A Dis. Mark. 21, 151–160 (2017).
doi: 10.3233/CBM-170462
Zhao, J. et al. LncRNA PVT1 promotes angiogenesis via activating the STAT3/VEGFA axis in gastric cancer. Oncogene 37, 4094–4109 (2018).
doi: 10.1038/s41388-018-0250-z
Li, Y. et al. Long non-coding RNA MALAT1 promotes gastric cancer tumorigenicity and metastasis by regulating vasculogenic mimicry and angiogenesis. Cancer Lett. 395, 31–44 (2017).
doi: 10.1016/j.canlet.2017.02.035
Song, W. et al. Identification of differentially expressed signatures of long non-coding RNAs associated with different metastatic potentials in gastric cancer. J. Gastroenterol. 51, 119–129 (2016).
doi: 10.1007/s00535-015-1091-y
Guo, H. & Xia, B. Collapsin response mediator protein 4 isoforms (CRMP4a and CRMP4b) have opposite effects on cell proliferation, migration, and invasion in gastric cancer. BMC Cancer 16, 565 (2016).
doi: 10.1186/s12885-016-2593-6
Xu, C. et al. SPP1, analyzed by bioinformatics methods, promotes the metastasis in colorectal cancer by activating EMT pathway. Biomed. Pharmacother. 91, 1167–1177 (2017).
doi: 10.1016/j.biopha.2017.05.056
Pan, Y., Jiao, G., Wang, C., Yang, J. & Yang, W. MicroRNA-421 inhibits breast cancer metastasis by targeting metastasis associated 1. Biomed. Pharmacother. 83, 1398–1406 (2016).
doi: 10.1016/j.biopha.2016.08.058
Li, C. et al. Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through regulation of the PI3K-Akt-mTOR signaling pathway. Oncotarget https://doi.org/10.18632/oncotarget.19281 (2017).
Lopez-Bergami, P. et al. c-Jun regulates phosphoinositide-dependent kinase 1 transcription: implication for Akt and protein kinase C activities and melanoma tumorigenesis. J. Biol. Chem. 285, 903–913 (2010).
doi: 10.1074/jbc.M109.075630
Xiao, Q. et al. Activation of ERK and mutual regulation of Stat3 and SP1 contribute to inhibition of PDK1 expression by atractylenolide-1 in human lung cancer cells. Cell. Physiol. Biochem. 43, 2353–2366 (2017).
doi: 10.1159/000484387
Picco, M. E. et al. STAT3 enhances the constitutive activity of AGC kinases in melanoma by transactivating PDK1. Cell Biosci. 9, 3 (2019).
doi: 10.1186/s13578-018-0265-8
Wang, Z. et al. SOX9-PDK1 axis is essential for glioma stem cell self-renewal and temozolomide resistance. Oncotarget 9, 192–204 (2018).
pubmed: 29416606
Xia, H. et al. EGFR-PI3K-PDK1 pathway regulates YAP signaling in hepatocellular carcinoma: the mechanism and its implications in targeted therapy. Cell Death Dis. 9, 269 (2018).
doi: 10.1038/s41419-018-0302-x
Huang, G. W., Zhang, Y. L., Liao, L. D., Li, E. M. & Xu, L. Y. Natural antisense transcript TPM1-AS regulates the alternative splicing of tropomyosin I through an interaction with RNA-binding motif protein 4. Int. J. Biochem. Cell Biol. 90, 59–67 (2017).
doi: 10.1016/j.biocel.2017.07.017
Peng, B. et al. Silencing of lncRNA AFAP1-AS1 suppressed lung cancer development by regulatory mechanism in cis and trans. Oncotarget 8, 93608–93623 (2017).
pubmed: 29212176
pmcid: 5706822
Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311–1323 (2007).
doi: 10.1016/j.cell.2007.05.022
Wu, B. et al. Down-regulation of lncTCF7 inhibits cell migration and invasion in colorectal cancer via inhibiting TCF7 expression. Hum. Cell https://doi.org/10.1007/s13577-018-0217-y (2018).
doi: 10.1007/s13577-018-0217-y
Zhang, C. L., Zhu, K. P. & Ma, X. L. Antisense lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2. Cancer Lett. 396, 66–75 (2017).
doi: 10.1016/j.canlet.2017.03.018
Wang, J. Y. et al. Expression and clinical significance of autophagic protein LC3B and EMT markers in gastric cancer. Cancer Manag. Res. 10, 1479–1486 (2018).
doi: 10.2147/CMAR.S164842
Zhou, L. H. et al. CircRNA_0023642 promotes migration and invasion of gastric cancer cells by regulating EMT. Eur. Rev. Med. Pharmacol. Sci. 22, 2297–2303 (2018).
pubmed: 29762831
Cui, H. et al. DNA methyltransferase 3A isoform b contributes to repressing E-cadherin through cooperation of DNA methylation and H3K27/H3K9 methylation in EMT-related metastasis of gastric cancer. Oncogene 37, 4358–4371 (2018).
doi: 10.1038/s41388-018-0285-1
Dong, P. et al. The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer. J. Transl. Med. 12, 231 (2014).
doi: 10.1186/s12967-014-0231-0
Morris, K. V. Long antisense non-coding RNAs function to direct epigenetic complexes that regulate transcription in human cells. Epigenetics 4, 296–301 (2009).
doi: 10.4161/epi.4.5.9282
Latge, G., Poulet, C., Bours, V., Josse, C. & Jerusalem, G. Natural Antisense transcripts: molecular mechanisms and implications in breast cancers. Int. J. Mol. Sci. https://doi.org/10.3390/ijms19010123 (2018).
doi: 10.3390/ijms19010123
Nie, L. et al. Long non-coding RNAs: versatile master regulators of gene expression and crucial players in cancer. Am. J. Transl. Res. 4, 127–150 (2012).
pubmed: 22611467
pmcid: 3353529
Muro, E. M. & Andrade-Navarro, M. A. Pseudogenes as an alternative source of natural antisense transcripts. BMC Evolut. Biol. 10, 338 (2010).
doi: 10.1186/1471-2148-10-338
Wang, Y. et al. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling. Cell Stem Cell 16, 413–425 (2015).
doi: 10.1016/j.stem.2015.03.003