Increasing evidence has suggested that long noncoding RNAs (lncRNAs) play critical roles in cancer development. Nasopharyngeal carcinoma (NPC) is a disease with high incidence. Although remarkable progress has been made in understanding the molecular mechanism and therapy strategies in NPC, the potential involvement of lncRNAs in NPC remains largely unknown. In this study, we identified that lncRNA cancer susceptibility candidate 9 (CASC9) is highly expressed in NPC tissues, which facilitates cell growth and is correlated with a poor prognosis of cancer patients. The underlying molecular mechanism revealed that CASC9 interacts with HIF1α and enhances the stabilization of HIF1α. Activation of HIF1α by overexpressed CASC9 promotes the glycolysis and tumorigenesis of NPC cells. Downregulation of CASC9 significantly inhibits NPC cancer cell growth. Collectively, our results illustrated the oncogenic role of CASC9 in promoting the progression of NPC through regulating HIF1α, which imply that modulation of CASC9 expression may be a promising target in cancer therapy.
Get full access to this article
View all access options for this article.
References
1.
ChenY.P., WangZ.X., ChenL., LiuX., TangL.L., MaoY.P., et al. (2015). A Bayesian network meta-analysis comparing concurrent chemoradiotherapy followed by adjuvant chemotherapy, concurrent chemoradiotherapy alone and radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. Ann Oncol, 26, 205–211.
2.
DepoixC.L., FlabatO., DebieveF., and HubinontC. (2016). HIF1A and EPAS1 mRNA and protein expression during in vitro culture of human primary term cytotrophoblasts and effect of oxygen tension on their expression. Reprod Biol, 16, 203–211.
3.
GeislerS., LojekL., KhalilA.M., BakerK.E., and CollerJ. (2012). Decapping of long noncoding RNAs regulates inducible genes. Mol Cell, 45, 279–291.
4.
IyerN.V., KotchL.E., AganiF., LeungS.W., LaughnerE., WengerR.H., et al. (1998). Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev, 12, 149–162.
5.
KhorkovaO., HsiaoJ., and WahlestedtC. (2015). Basic biology and therapeutic implications of lncRNA. Adv Drug Deliv Rev, 87, 15–24.
6.
LeeG., WonH.S., LeeY.M., ChoiJ.W., OhT.I., JangJ.H., et al. (2016). Oxidative dimerization of PHD2 is responsible for its inactivation and contributes to metabolic reprogramming via HIF-1alpha activationv. Sci Rep, 6, 18928.
7.
LinA., LiC., XingZ., HuQ., LiangK., HanL., et al. (2016). The LINK-A lncRNA activates normoxic HIF1alpha signalling in triple-negative breast cancer. Nat Cell Biol, 18, 213–224.
8.
LottinS., AdriaenssensE., DupressoirT., BerteauxN., MontpellierC., CollJ., et al. (2002). Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells. Carcinogenesis, 23, 1885–1895.
NakazawaM.S., KeithB., and SimonM.C. (2016). Oxygen availability and metabolic adaptations. Nat Rev Cancer, 16, 663–673.
11.
NishidaY., RardinM.J., CarricoC., HeW., SahuA.K., GutP., et al. (2015). SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol Cell, 59, 321–332.
12.
OromU.A., DerrienT., BeringerM., GumireddyK., GardiniA., BussottiG., et al. (2010). Long noncoding RNAs with enhancer-like function in human cells. Cell, 143, 46–58.
13.
PanZ., MaoW., BaoY., ZhangM., SuX., and XuX. (2016). The long noncoding RNA CASC9 regulates migration and invasion in esophageal cancer. Cancer Med, 5, 2442–2447.
14.
PavlovaN.N., and ThompsonC.B. (2016). The emerging hallmarks of cancer metabolism. Cell Metab, 23, 27–47.
15.
PontingC.P., OliverP.L., and ReikW. (2009). Evolution and functions of long noncoding RNAs. Cell, 136, 629–641.
16.
SchmittA.M., and ChangH.Y. (2016). Long noncoding RNAs in cancer pathways. Cancer Cell, 29, 452–463.
17.
ShiS.J., WangL.J., YuB., LiY.H., JinY., and BaiX.Z. (2015). LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget, 6, 11652–11663.
18.
SlemcL., and KunejT. (2016). Transcription factor HIF1A: downstream targets, associated pathways, polymorphic hypoxia response element (HRE) sites, and initiative for standardization of reporting in scientific literature. Tumour Biol, 37, 14851–14861.
19.
SongP., and YinS.C. (2016). Long non-coding RNA EWSAT1 promotes human nasopharyngeal carcinoma cell growth in vitro by targeting miR-326/-330-5p. Aging, 8, 2948–2960.
20.
SunL., YangC., XuJ., FengY., WangL., and CuiT. (2016). Long noncoding RNA EWSAT1 promotes osteosarcoma cell growth and metastasis through suppression of MEG3 expression. DNA Cell Biol, 35, 812–818.
21.
WangF., YuanJ.H., WangS.B., YangF., YuanS.X., YeC., et al. (2014). Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatology, 60, 1278–1290.
22.
WeiK.R., ZhengR.S., ZhangS.W., LiangZ.H., OuZ.X., and ChenW.Q. (2014). Nasopharyngeal carcinoma incidence and mortality in China in 2010. Chin J Cancer, 33, 381–387.
23.
YoungL.S., and RickinsonA.B. (2004). Epstein-Barr virus: 40 years on. Nat Rev Cancer, 4, 757–768.
24.
YuanS.X., WangJ., YangF., TaoQ.F., ZhangJ., WangL.L., et al. (2016). Long noncoding RNA DANCR increases stemness features of hepatocellular carcinoma by derepression of CTNNB1. Hepatology, 63, 499–511.
25.
ZhangZ., WeaverD.L., OlsenD., deKayJ., PengZ., AshikagaT., et al. (2016). Long non-coding RNA chromogenic in situ hybridisation signal pattern correlation with breast tumour pathology. J Clin Pathol, 69, 76–81.
