Abstract
Objective and design
We investigated the expressions of lncRNA MEG3 and PTEN in ovarian cancer tissues and their effects on cell proliferation, cycle and apoptosis of ovarian cancer.
Methods
Expression levels of MEG3 in ovarian cancer cell lines and normal ovarian cell lines were detected by qRT-PCR. Cell viability was detected by MTT assay. Cell apoptosis and cell cycle distribution were measured by flow cytometry. Cell invasion capability was tested by transwell assay. Cell migration capacity was tested by wound healing. The xenograft model was constructed to explore the effect of lncRNA MEG3 on ovarian cancer in vivo.
Result
Compared with normal ovarian cells, expression levels of MEG3 and PTEN were relatively lower in ovarian cancer cells. There was a positive correlation between the expression of PTEN and the expression of MEG3. Enhanced expression level of PTEN suppressed SKOV3 cell proliferation, increased cell apoptosis rate, and decreased cell invasion and migration.
Conclusion
LncRNA MEG3 and PTEN were down-regulated in ovarian cancer cells. LncRNA MEG3 regulated the downstream gene PTEN in ovarian cancer cells to prohibit cell proliferation, promote apoptosis and block cell cycle progression.
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Abbreviations
- ANOVA:
-
Analysis of variance
- lncRNAs:
-
Long non-coding RNAs
- MEG3:
-
Maternally expressed 3 gene
- nt:
-
Nucleotides
- PI3K:
-
Phosphatidylinositol-3-kinase
References
Bruney L, Liu Y, Grisoli A, Ravosa MJ, Stack MS. Integrin-linked kinase activity modulates the pro-metastatic behavior of ovarian cancer cells. Oncotarget. 2016;7:21968–81.
Itamochi H. Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action. World J Biol Chem. 2010;1:209–20.
Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.
Yu X, Li Z. Long non-coding RNA HOTAIR: a novel oncogene (review). Mol Med Rep. 2015;12:5611–8.
Meseure D, Drak Alsibai K, Nicolas A, Bieche I, Morillon A. long noncoding RNAs as new architects in cancer epigenetics, prognostic biomarkers, and potential therapeutic targets. Biomed Res Int 2015; 2015:320214.
Cui L, Xie XY, Wang H, Chen XL, Liu SL, Hu LN. Expression of long non-coding RNA HOTAIR mRNA in ovarian cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2013;44:57–9.
Yang SL, Lin RX, Si LH, Cui MH, Zhang XW, Fan LM. Expression and functional role of long non-coding RNA AFAP1-AS1 in ovarian cancer. Eur Rev Med Pharmacol Sci. 2016;20:5107–12.
Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, et al. Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells. 2000;5:211–20.
Sun L, Li Y, Yang B. Downregulated long non-coding RNA MEG3 in breast cancer regulates proliferation, migration and invasion by depending on p53’s transcriptional activity. Biochem Biophys Res Commun. 2016;478:323–9.
Qin R, Chen Z, Ding Y, Hao J, Hu J, Guo F. Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma. 2013;60:486–92.
Sun M, Xia R, Jin F, Xu T, Liu Z, De W, et al. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer. Tumour Biol. 2014;35:1065–73.
Yin DD, Liu ZJ, Zhang E, Kong R, Zhang ZH, Guo RH. Decreased expression of long noncoding RNA MEG3 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Tumour Biol. 2015;36:4851–9.
Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, et al. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 2013;13:461.
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–7.
Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 2001;114:2375–82.
Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell. 2000;100:387–90.
Goberdhan DC, Wilson C. PTEN: tumour suppressor, multifunctional growth regulator and more. Hum Mol Genet. 2003;2:R239–R248 (12 Spec No).
Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92:924–30.
Zhang J, Yao T, Wang Y, Yu J, Liu Y, Lin Z. Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21. Cancer Biol Ther. 2016;17:104–13.
Zhang CY, Yu MS, Li X, Zhang Z, Han CR, Yan B. Overexpression of long non-coding RNA MEG3 suppresses breast cancer cell proliferation, invasion, and angiogenesis through AKT pathway. Tumour Biol. 2017;39:1010428317701311.
Wu XS, Wang XA, Wu WG, Hu YP, Li ML, Ding Q, et al. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther. 2014;15:806–14.
Xiu YL, Sun KX, Chen X, Chen S, Zhao Y, Guo QG, et al. Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and progression of epithelial ovarian carcinoma by regulating activity of ATG3. Oncotarget. 2017;8:31714–25.
Sheng X, Li J, Yang L, Chen Z, Zhao Q, Tan L, et al. Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer. Oncol Rep. 2014;32:277–85.
Zhang J, Liu J, Xu X, Li L. Curcumin suppresses cisplatin resistance development partly via modulating extracellular vesicle-mediated transfer of MEG3 and miR-214 in ovarian cancer. Cancer Chemother Pharmacol. 2017;79:479–87.
Tanwar PS, Kaneko-Tarui T, Lee HJ, Zhang L, Teixeira JM. PTEN loss and HOXA10 expression are associated with ovarian endometrioid adenocarcinoma differentiation and progression. Carcinogenesis. 2013;34:893–901.
Martins FC, Santiago I, Trinh A, Xian J, Guo A, Sayal K, et al. Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier. Genome Biol. 2014;15:526.
Shen W, Li HL, Liu L, Cheng JX. Expression levels of PTEN, HIF-1alpha, and VEGF as prognostic factors in ovarian cancer. Eur Rev Med Pharmacol Sci. 2017;21:2596–603.
Wang L, Wang C, Jin S, Qu D, Ying H. Expression of NF-kappaB and PTEN in primary epithelial ovarian carcinoma and the correlation with chemoresistance. Int J Clin Exp Pathol. 2015;8:10953–63.
Tanwar PS, Mohapatra G, Chiang S, Engler DA, Zhang L, Kaneko-Tarui T, et al. Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer. Carcinogenesis. 2014;35:546–53.
Li J, Hu K, Gong G, Zhu D, Wang Y, Liu H, et al. Upregulation of MiR-205 transcriptionally suppresses SMAD4 and PTEN and contributes to human ovarian cancer progression. Sci Rep. 2017;7:41330.
Liu H, Pan Y, Han X, Liu J, Li R. MicroRNA-216a promotes the metastasis and epithelial-mesenchymal transition of ovarian cancer by suppressing the PTEN/AKT pathway. Onco Targets Ther. 2017;10:2701–9.
Fang Y, Xu C, Fu Y. MicroRNA-17-5p induces drug resistance and invasion of ovarian carcinoma cells by targeting PTEN signaling. J Biol Res (Thessalon). 2015;22:12.
Yang NQ, Luo XJ, Zhang J, Wang GM, Guo JM. Crosstalk between Meg3 and miR-1297 regulates growth of testicular germ cell tumor through PTEN/PI3K/AKT pathway. Am J Transl Res. 2016;8:1091–9.
Liu Z, Ren YA, Pangas SA, Adams J, Zhou W, Castrillon DH, et al. FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development. Mol Endocrinol. 2015;29:1006–24.
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JW and WX: critical revision of the manuscript; YH and QX: substantial contribution to the conception and design of the work, and manuscript drafting; QX and YH: acquisition, analysis, and interpretation of the data; SL: revising the manuscript critically and final approval of the version to be published. All authors have read and approved the final article.
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All procedures performed in studies involving animals were in accordance with the ethical standards of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Responsible Editor: John Di Battista.
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Wang, J., Xu, W., He, Y. et al. LncRNA MEG3 impacts proliferation, invasion, and migration of ovarian cancer cells through regulating PTEN. Inflamm. Res. 67, 927–936 (2018). https://doi.org/10.1007/s00011-018-1186-z
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DOI: https://doi.org/10.1007/s00011-018-1186-z