Long non-coding RNA BACE1-AS is a novel target for anisomycin-mediated suppression of ovarian cancer stem cell proliferation and invasion

Chen,Qing; Liu,Xinghui; Xu,Limin; Wang,Ying; Wang,Suwei; Li,Qiong; Huang,Yongyi; Liu,Te

doi:10.3892/or.2016.4571

Long non-coding RNA BACE1-AS is a novel target for anisomycin-mediated suppression of ovarian cancer stem cell proliferation and invasion

Authors:
- Qing Chen
- Xinghui Liu
- Limin Xu
- Ying Wang
- Suwei Wang
- Qiong Li
- Yongyi Huang
- Te Liu
View Affiliations

Affiliations: Gongli Hospital Affiliated to The Second Military Medical University in Pudong New Area of Shanghai City, Shanghai 200135, P.R. China, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
Published online on: January 18, 2016 https://doi.org/10.3892/or.2016.4571
Pages: 1916-1924

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Human ovarian cancer stem cells (OCSCs) are one of the main factors affecting ovarian cancer cell metastasis, recurrence, prognosis and tolerance to chemotherapy drugs. However, the mechanisms of OCSC proliferation and invasion are not clear. Recent studies suggest that anisomycin can inhibit the proliferative and invasive ability of various tumor cells by increasing the production of the toxic amyloid β (Aβ1-42) peptides from the amyloid precursor protein (APP). We explored whether anisomycin could also suppress human OCSC proliferation and invasion. The CD44+/CD117+ OCSCs were enriched from human clinical ovarian tumor tissues. OCSCs treated with anisomycin showed reduced proliferation compared to controls. Moreover, anisomycin significantly suppressed the invasive capacity of OCSCs in vitro, as indicated by cell migration assays. The mRNA expression levels of long non-coding RNA (lncRNA) β-site APP cleaving enzyme 1 antisense strand (BACE1-AS) were significantly increased in anisomycin-treated OCSCs compared to controls. In addition, mRNA and protein levels of BACE1 and Aβ1-42 were increased in anisomycin-treated OCSCs compared to controls. We confirmed that anisomycin suppressed the growth of xenograft tumors formed by OCSCs in vivo. Finally, when expression of lncRNA BACE1-AS was silenced using siRNA, BACE1 expression was downregulated and the antiproliferative and anti-invasive effects of anisomycin were reduced. Overall, we identified lncRNA BACE1-AS as a novel target for anisomycin. Elevation of lncRNA BACE1-AS expression is a potential mechanism for suppressing human OCSC proliferation and invasion.

View Figures

View References

1	Cheng W, Liu T, Wan X, Gao Y and Wang H: MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J. 279:2047–2059. 2012. View Article : Google Scholar : PubMed/NCBI
2	Høgdall E, Fung ET, Christensen IJ, Yip C, Nedergaard L, Engelholm SA, Risum S, Petri AL, Lundvall L, Lomas L, et al: Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients. Proteomics Clin Appl. 4:940–952. 2010. View Article : Google Scholar : PubMed/NCBI
3	Liu T, Cheng W, Lai D, Huang Y and Guo L: Characterization of primary ovarian cancer cells in different culture systems. Oncol Rep. 23:1277–1284. 2010.PubMed/NCBI
4	Liu T, Hou L and Huang Y: EZH2-specific microRNA-98 inhibits human ovarian cancer stem cell proliferation via regulating the pRb-E2F pathway. Tumour Biol. 35:7239–7247. 2014. View Article : Google Scholar : PubMed/NCBI
5	Liu T, Qin W, Hou L and Huang Y: MicroRNA-17 promotes normal ovarian cancer cells to cancer stem cells development via suppression of the LKB1-p53-p21/WAF1 pathway. Tumour Biol. 36:1881–1893. 2015. View Article : Google Scholar
6	Ma L, Lai D, Liu T, Cheng W and Guo L: Cancer stem-like cells can be isolated with drug selection in human ovarian cancer cell line SKOV3. Acta Biochim Biophys Sin. 42:593–602. 2010. View Article : Google Scholar : PubMed/NCBI
7	Qin W, Ren Q, Liu T, Huang Y and Wang J: MicroRNA-155 is a novel suppressor of ovarian cancer-initiating cells that targets CLDN1. FEBS Lett. 587:1434–1439. 2013. View Article : Google Scholar : PubMed/NCBI
8	Yu ZH, Liu T, Zhao YH, Huang YY and Gao YT: Cisplatin targets the stromal cell-derived factor-1-CXC chemokine receptor type 4 axis to suppress metastasis and invasion of ovarian cancer-initiating cells. Tumour Biol. 35:4637–4644. 2014. View Article : Google Scholar : PubMed/NCBI
9	Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH and Nephew KP: Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 68:4311–4320. 2008. View Article : Google Scholar : PubMed/NCBI
10	Guo X, Wu X, Ren L, Liu G and Li L: Epigenetic mechanisms of amyloid-β production in anisomycin-treated SH-SY5Y cells. Neuroscience. 194:272–281. 2011. View Article : Google Scholar : PubMed/NCBI
11	Fan X, Liu Y, Jiang J, Ma Z, Wu H, Liu T, Liu M and Lixand Tang H: miR-20a promotes proliferation and invasion by targeting APP in human ovarian cancer cells. Acta Biochim Biophys Sin. 42:318–324. 2010. View Article : Google Scholar : PubMed/NCBI
12	Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G III, Kenny PJ and Wahlestedt C: Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 14:723–730. 2008. View Article : Google Scholar : PubMed/NCBI
13	Liu T, Huang Y, Chen J, Chi H, Yu Z, Wang J and Chen C: Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1-AS expression. Mol Med Rep. 10:1275–1281. 2014.PubMed/NCBI
14	Yan R and Vassar R: Targeting the β secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 13:319–329. 2014. View Article : Google Scholar : PubMed/NCBI
15	Liu Y, Ge J, Li Q, Gu L, Guo X, Ma ZG and Zhu YP: Anisomycin induces apoptosis of glucocorticoid resistant acute lymphoblastic leukemia CEM-C1 cells via activation of mitogen-activated protein kinases p38 and JNK. Neoplasma. 60:101–110. 2013. View Article : Google Scholar
16	Feng Y, Liu T, Li XQ, Liu Y, Zhu XY, Jankovic J, Pan TH and Wu YC: Neuroprotection by Orexin-A via HIF-1α induction in a cellular model of Parkinson's disease. Neurosci Lett. 579:35–40. 2014. View Article : Google Scholar : PubMed/NCBI
17	Yu C, Xing F, Tang Z, Bronner C, Lu X, Di J, Zeng S and Liu J: Anisomycin suppresses Jurkat T cell growth by the cell cycle-regulating proteins. Pharmacol Rep. 65:435–444. 2013. View Article : Google Scholar : PubMed/NCBI
18	Seo BR, Min KJ, Kim S, Park JW, Park WK, Lee TJ and Kwon TK: Anisomycin treatment enhances TRAIL-mediated apoptosis in renal carcinoma cells through the down-regulation of Bcl-2, c-FLIP(L) and Mcl-1. Biochimie. 95:858–865. 2013. View Article : Google Scholar
19	Li JY, Huang JY, Li M, Zhang H, Xing B, Chen G, Wei D, Gu PY and Hu WX: Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro. Acta Pharmacol Sin. 33:935–940. 2012. View Article : Google Scholar : PubMed/NCBI
20	Hébert SS, Serneels L, Tolia A, Craessaerts K, Derks C, Filippov MA, Müller U and De Strooper B: Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes. EMBO Rep. 7:739–745. 2006. View Article : Google Scholar : PubMed/NCBI
21	Laird FM, Cai H, Savonenko AV, Farah MH, He K, Melnikova T, Wen H, Chiang HC, Xu G, Koliatsos VE, et al: BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci. 25:11693–11709. 2005. View Article : Google Scholar : PubMed/NCBI
22	Ohno M, Sametsky EA, Younkin LH, Oakley H, Younkin SG, Citron M, Vassar R and Disterhoft JF: BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron. 41:27–33. 2004. View Article : Google Scholar : PubMed/NCBI
23	Luo Y, Bolon B, Damore MA, Fitzpatrick D, Liu H, Zhang J, Yan Q, Vassar R and Citron M: BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time. Neurobiol Dis. 14:81–88. 2003. View Article : Google Scholar : PubMed/NCBI
24	Dominguez D, Tournoy J, Hartmann D, Huth T, Cryns K, Deforce S, Serneels L, Camacho IE, Marjaux E, Craessaerts K, et al: Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. J Biol Chem. 280:30797–30806. 2005. View Article : Google Scholar : PubMed/NCBI
25	Luo Y, Bolon B, Kahn S, Bennett BD, Babu-Khan S, Denis P, Fan W, Kha H, Zhang J, Gong Y, et al: Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat Neurosci. 4:231–232. 2001. View Article : Google Scholar : PubMed/NCBI