Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer

Lou,Yanhui; Jiang,Huanhuan; Cui,Zhumei; Wang,Xiangyu; Wang,Lingzhi; Han,Yi

doi:10.3892/ijmm.2018.3588

Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer

Authors:
- Yanhui Lou
- Huanhuan Jiang
- Zhumei Cui
- Xiangyu Wang
- Lingzhi Wang
- Yi Han
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Affiliations: Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
Published online on: March 23, 2018 https://doi.org/10.3892/ijmm.2018.3588
Pages: 91-104
Copyright: © Lou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

High‑grade ovarian serous cancer is known for its high rates of invasion and metastasis, and resultant high mortality rate. Therefore, research concerning biomarkers and underlying molecular mechanisms of high‑grade ovarian serous cancer progression and prognosis are urgently required. Long non‑coding RNAs (lncRNAs) have been the subject of an increasing number of studies, and certain lncRNAs have been demonstrated to serve an important function in the development and progression of various cancers, including HOX transcript antisense RNA, competing endogenous lncRNA 2 for microRNA let‑7b, urothelial cancer associated 1, and H19, imprinted maternally expressed transcript (non‑protein coding). However, few studies have investigated the differential expression of lncRNAs in high‑grade ovarian serous cancer. In the present study, differences in lncRNA and mRNA expression profiles between high‑grade ovarian serous cancer tissue samples and healthy fallopian tube tissue samples were investigated using microarray analysis, and the differential expression of lncRNAs and mRNAs was confirmed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Then, five abnormally expressed lncRNAs were selected, and the associations between these lncRNAs and ovarian cancer clinicopathological parameters were examined using RT‑qPCR. The expression profiles of certain lncRNAs and mRNAs were confirmed to be altered between high‑grade ovarian serous cancer tissues and healthy fallopian tube tissues. Furthermore, the expression levels of selected lncRNAs were associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. These lncRNAs and mRNAs may therefore be involved in the pathogenesis of high‑grade ovarian serous cancer. The results of the present study provide an experimental foundation for further exploration of the value of these lncRNAs and mRNAs in the early diagnosis and treatment of high‑grade ovarian serous cancer.

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1	Bast RC Jr, Hennessy B and Mills GB: The biology of ovarian cancer: New opportunities for translation. Nat Rev Cancer. 9:415–428. 2009. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
3	Yiwei T, Hua H, Hui G, Mao M and Xiang L: HOTAIR interacting with MAPK1 regulates ovarian cancer skov3 cell proliferation, migration, and invasion. Med Sci Monit. 21:1856–1863. 2015. View Article : Google Scholar : PubMed/NCBI
4	ENCODE Project Consortium; Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, et al: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 447:799–816. 2007. View Article : Google Scholar : PubMed/NCBI
5	Nagano T and Fraser P: No-nonsense functions for long noncoding RNAs. Cell. 145:178–181. 2011. View Article : Google Scholar : PubMed/NCBI
6	Yang Q, Xu E, Dai J, Liu B, Han Z, Wu J, Zhang S, Peng B, Zhang Y and Jiang Y: A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 285:79–88. 2015. View Article : Google Scholar : PubMed/NCBI
7	Gibb EA, Brown CJ and Lam WL: The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 10:382011. View Article : Google Scholar : PubMed/NCBI
8	Zhang H, Chen Z, Wang X, Huang Z, He Z and Chen Y: Long non-coding RNA: A new player in cancer. J Hematol Oncol. 6:372013. View Article : Google Scholar : PubMed/NCBI
9	Tang SC and Chen YC: Novel therapeutic targets for pancreatic cancer. World J Gastroenterol. 20:10825–10844. 2014. View Article : Google Scholar : PubMed/NCBI
10	Zeng Z, Bo H, Gong Z, Lian Y, Li X, Li X, Zhang W, Deng H, Zhou M, Peng S, et al: AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis. Tumour Biol. 37:729–737. 2016. View Article : Google Scholar
11	Qiu JJ, Wang Y, Ding JX, Jin HY, Yang G and Hua KQ: The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis. Exp Cell Res. 333:238–248. 2015. View Article : Google Scholar : PubMed/NCBI
12	Ono H, Motoi N, Nagano H, Miyauchi E, Ushijima M, Matsuura M, Okumura S, Nishio M, Hirose T, Inase N and Ishikawa Y: Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer. Cancer Med. 3:632–642. 2014. View Article : Google Scholar : PubMed/NCBI
13	Han Y, Liu Y, Zhang H, Wang T, Diao R, Jiang Z, Gui Y and Cai Z: Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long noncoding RNA MALAT1. FEBS Lett. 587:3875–3882. 2013. View Article : Google Scholar
14	Hou P, Zhao Y, Li Z, Yao R, Ma M, Gao Y, Zhao L, Zhang Y, Huang B and Lu J: LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell Death Dis. 5:e12872014. View Article : Google Scholar : PubMed/NCBI
15	Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, Xu TP, Xia R, Yang JS, De W and Chen Jf: Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget. 5:2276–2292. 2014. View Article : Google Scholar :
16	Xia T, Chen S, Jiang Z, Shao Y, Jiang X, Li P, Xiao B and Guo J: Long noncoding RNA FER1L4 suppresses cancer cell growth by acting as a competing endogenous RNA and regulating PTEN expression. Sci Rep. 5:134452015. View Article : Google Scholar : PubMed/NCBI
17	Qiu JJ, Lin YY, Ye LC, Ding JX, Feng WW, Jin HY, Zhang Y, Li Q and Hua KQ: Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol. 134:121–128. 2014. View Article : Google Scholar : PubMed/NCBI
18	Richards EJ, Permuth-Wey J, Li Y, Chen YA, Coppola D, Reid BM, Lin HY, Teer JK, Berchuck A, Birrer MJ, et al: A functional variant in HOXA11-AS, a novel long non-coding RNA, inhibits the oncogenic phenotype of epithelial ovarian cancer. Oncotarget. 6:34745–34757. 2015. View Article : Google Scholar : PubMed/NCBI
19	Gao Y, Meng H, Liu S, Hu J, Zhang Y, Jiao T, Liu Y, Ou J, Wang D, Yao L, et al: LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b. Hum Mol Genet. 24:841–852. 2015. View Article : Google Scholar
20	Li J, Zhou D, Wang Z, Tan L, Zhou Y, Li J and Sheng X: Reversal effect of 5-aza-2-deoxycytidine on the maternally expressed gene 3 promoter hypermethylation and its inhibitory effect on the proliferation of epithelial ovarian cancer cells. Zhonghua Zhong Liu Za Zhi. 37:324–329. 2015.In Chinese. PubMed/NCBI
21	Yang Y, Jiang Y, Wan Y, Zhang L, Qiu J, Zhou S and Cheng W: UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis. Tumour Biol. 37:10633–10641. 2016. View Article : Google Scholar : PubMed/NCBI
22	Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 25:25–29. 2000. View Article : Google Scholar : PubMed/NCBI
23	The Gene Ontology Consortium: Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res. 45(D1): D331–D338. 2017. View Article : Google Scholar :
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
25	Kanehisa M and Goto S: KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000. View Article : Google Scholar
26	Darryl N: Biotech Software & Internet Report 2. 117–120. 2004.
27	Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, Haw R, Jassal B, Korninger F, May B, et al: The reactome pathway knowledgebase. Nucleic Acids Res. 46(D1): D649–D655. 2018. View Article : Google Scholar :
28	Milacic M, Haw R, Rothfels K, Wu G, Croft D, Hermjakob H, D'Eustachio P and Stein L: Annotating cancer variants and anti-cancer therapeutics in reactome. Cancers (Basel). 4:1180–1211. 2012. View Article : Google Scholar
29	Yang Y, Li H, Hou S, Hu B, Liu J and Wang J: The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 8:e653092013. View Article : Google Scholar : PubMed/NCBI
30	Cao G, Zhang J, Wang M, Song X, Liu W, Mao C and Lv C: Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis. Int J Mol Med. 32:355-3642013. View Article : Google Scholar
31	Tsai MC, Spitale RC and Chang HY: Long intergenic noncoding RNAs: New links in cancer progression. Cancer Res. 71:3–7. 2011. View Article : Google Scholar : PubMed/NCBI
32	Cohen M, Pierredon S, Wuillemin C, Delie F and Petignat P: Acellular fraction of ovarian cancer ascites induce apoptosis by activating JNK and inducing BRCA1, Fas and FasL expression in ovarian cancer cells. Oncoscience. 1:262–271. 2014. View Article : Google Scholar
33	Hayano T, Yokota Y, Hosomichi K, Nakaoka H, Yoshihara K, Adachi S, Kashima K, Tsuda H, Moriya T, Tanaka K, et al: Molecular characterization of an intact p53 pathway subtype in high-grade serous ovarian cancer. PLoS One. 9:e1144912014. View Article : Google Scholar : PubMed/NCBI
34	Li J, Hu K, Gong G, Zhu D, Wang Y, Liu H and Wu X: Upregulation of MiR-205 transcriptionally suppresses SMAD4 and PTEN and contributes to human ovarian cancer progression. Sci Rep. 7:413302017. View Article : Google Scholar : PubMed/NCBI
35	Bugide S, Gonugunta VK, Penugurti V, Malisetty VL, Vadlamudi RK and Manavathi B: HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation. Cell Oncol (Dordr). 40:133–144. 2017. View Article : Google Scholar
36	Zeppernick F and Meinhold-Heerlein I: The new FIGO staging system for ovarian, fallopian tube, and primary peritoneal cancer. Arch Gynecol Obstet. 290:839–842. 2014. View Article : Google Scholar : PubMed/NCBI
37	Jelovac D: Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 61:183–203. 2011. View Article : Google Scholar : PubMed/NCBI
38	Ji Q, Zhang L, Liu X, Zhou L, Wang W, Han Z, Sui H, Tang Y, Wang Y, Liu N, et al: Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/TBP2 complex. Br J Cancer. 111:736–748. 2014. View Article : Google Scholar : PubMed/NCBI
39	Shi Y, Liu Y, Wang J, Jie D, Yun T, Li W, Yan L, Wang K and Feng J: Downregulated long noncoding RNA BANCR promotes the proliferation of colorectal cancer cells via downregualtion of p21 expression. PLoS One. 10:e01226792015. View Article : Google Scholar : PubMed/NCBI
40	Xue M, Li X, Li Z and Chen W: Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1alpha-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol. 35:6901–6912. 2014. View Article : Google Scholar : PubMed/NCBI
41	Srivastava AK, Singh PK, Rath SK, Dalela D, Goel MM and Bhatt ML: Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder. Tumour Biol. 35:11435–11442. 2014. View Article : Google Scholar : PubMed/NCBI
42	Wang F, Ren S, Chen R, Lu J, Shi X, Zhu Y, Zhang W, Jing T, Zhang C, Shen J, et al: Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer. Oncotarget. 5:11091–11102. 2014.PubMed/NCBI
43	Yin D, He X, Zhang E, Kong R, De W and Zhang Z: Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol. 31:2532014. View Article : Google Scholar : PubMed/NCBI
44	Yang M, Zhai X, Xia B, Wang Y and Lou G: Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA. Tumour Biol. 36:7615–7622. 2015. View Article : Google Scholar : PubMed/NCBI
45	Li H, Li J, Jia S, Wu M, An J, Zheng Q, Zhang W and Lu D: miR675 upregulates long noncoding RNA H19 through activating EGR1 in human liver cancer. Oncotarget. 6:31958–31984. 2015.PubMed/NCBI
46	Qu S, Yang X, Song W, Sun W, Li X, Wang J, Zhong Y, Shang R, Ruan B, Zhang Z, et al: Downregulation of lncRNA-ATB correlates with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. 37:3933–3938. 2016. View Article : Google Scholar
47	Zhou J, Li W, Jin T, Xiang X, Li M, Wang J, Li G, Pan X and Lei D: Gene microarray analysis of lncRNA and mRNA expression profiles in patients with hypopharyngeal squamous cell carcinoma. Int J Clin Exp Med. 8:4862–4882. 2015.PubMed/NCBI
48	Zhou M, Ye Z, Gu Y, Tian B, Wu B and Li J: Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling. Int J Clin Exp Pathol. 8:38–52. 2015.PubMed/NCBI
49	Yang L, Zhang J, Jiang A, Liu Q, Li C, Yang C and Xiu J: Expression profile of long non-coding RNAs is altered in endometrial cancer. Int J Clin Exp Med. 8:5010–5021. 2015.PubMed/NCBI
50	Yang QQ and Deng YF: Genome-wide analysis of long non-coding RNA in primary nasopharyngeal carcinoma by microarray. Histopathology. 66:1022–1030. 2015. View Article : Google Scholar
51	Xie M, Sun M, Zhu YN, Xia R, Liu YW, Ding J, Ma HW, He XZ, Zhang ZH, Liu ZJ, et al: Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/LK3/DDIT3 expression. Oncotarget. 6:33587–33601. 2015. View Article : Google Scholar : PubMed/NCBI
52	Zhou X, Gao Q, Wang J, Zhang X, Liu K and Duan Z: Linc-RNA-RoR acts as a 'sponge' against mediation of the differentiation of endometrial cancer stem cells by microRNA-145. Gynecol Oncol. 133:333–339. 2014. View Article : Google Scholar : PubMed/NCBI
53	Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, et al: Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA. 106:11667–11672. 2009. View Article : Google Scholar : PubMed/NCBI
54	Mattick JS and Gagen MJ: The evolution of controlled multi-tasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms. Mol Biol Evol. 18:1611–1630. 2001. View Article : Google Scholar : PubMed/NCBI
55	Popadin K, Gutierrez-Arcelus M, Dermitzakis ET and Antonarakis SE: Genetic and epigenetic regulation of human lincRNA gene expression. Am J Hum Genet. 93:1015–1026. 2013. View Article : Google Scholar : PubMed/NCBI