A novel lncRNA, Lnc-OC1, promotes ovarian cancer cell proliferation and migration by sponging miR-34a and miR-34c

Fangfang Tao; Xinxin Tian; Mengxi Lu; Zhiqian Zhang

doi:10.1016/j.jgg.2018.03.001

Volume 45 Issue 3

Mar. 2018

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Article Navigation > Journal of Genetics and Genomics > 2018 > 45(3): 137-145

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A novel lncRNA, Lnc-OC1, promotes ovarian cancer cell proliferation and migration by sponging miR-34a and miR-34c

doi: 10.1016/j.jgg.2018.03.001

Fangfang Tao^{a, #},
Xinxin Tian^{b, c, #},
Mengxi Lu^{d, #},
Zhiqian Zhang^{b, e}

a
Department of Immunology and Microbiology, Basic Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
b
Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China
c
Department of Biochemistry and Biophysics, Texas A&M University and Texas AgriLife Research, College Station, TX 77843-2128, USA
d
North China University of Science and Technology, Tangshan 063210, China
e
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

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Corresponding author: E-mail address: zhangzhiqian@tjab.org (Zhiqian Zhang)
Received Date: 2017-10-10
Accepted Date: 2018-03-04
Rev Recd Date: 2018-03-01

Available Online: 2018-03-06

Publish Date: 2018-03-20

Abstract

Abstract

Long non-coding RNAs (lncRNAs) have been reported to be of great importance in tumorigenesis and progression of a variety of cancers. However, the role of lncRNAs in ovarian cancer (OC) remains largely unknown. In the present study, we identified a novel lncRNA, LOC100288181 (named as Lnc-OC1), which acted as a key regulator in the development and progression of OC. The combined Gene Expression Omnibus (GEO) database analysis revealed that Lnc-OC1 was significantly upregulated in OC tissues and Kaplan-Meier survival analysis confirmed that high Lnc-OC1 expression was associated with poor prognosis of OC patients. Importantly, we also demonstrated that knockdown of Lnc-OC1 suppressed cell proliferation, colony formation, invasion and migrationin vitro and inhibited tumorigenicity in vivo. Mechanistically, Lnc-OC1 repressed the expression of endogenous miR-34a and miR-34c as a sponge and vice versa. Moreover, rescue experiments demonstrated that the oncogenic function of Lnc-OC1 at least partially depended on suppressing miR-34a and miR-34c. In conclusion, our results suggest that the Lnc-OC1-miR-34a/34c axis may play a pivotal role in OC, and may serve as a potential diagnostic biomarker and a powerful therapeutic target for OC.
- Ovarian cancer,
- Lnc-OC1,
- miR-34a,
- miR-34c,
- Tumorigenicity

These three authors contributed equally to this work.

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References(27)

References

[1]	Cheng, C.Y., Hwang, C.I., Corney, D.C. et al. miR-34 cooperates with p53 in suppression of prostate cancer by joint regulation of stem cell compartment Cell Rep., 6 (2014),pp. 1000-1007
[2]	Cortez, M.A., Ivan, C., Valdecanas, D. et al. PDL1 regulation by p53 via miR-34 J. Natl. Cancer Inst., 108 (2016)
[3]	Dong, L., Hui, L. HOTAIR promotes proliferation, migration, and invasion of ovarian cancer SKOV3 cells through regulating PIK3R3 Med. Sci. Mon., 22 (2016),pp. 325-331
[4]	Elgaaen, B.V., Olstad, O.K., Sandvik, L. et al. PLoS One, 7 (2012)
[5]	Hermeking, H. The miR-34 family in cancer and apoptosis Cell Death Differ., 17 (2010),pp. 193-199
[6]	Huang, S., Qing, C., Huang, Z. et al. The long non-coding RNA CCAT2 is up-regulated in ovarian cancer and associated with poor prognosis Diagn. Pathol., 11 (2016),p. 49
[7]	Hwang, C.I., Matoso, A., Corney, D.C. et al. Wild-type p53 controls cell motility and invasion by dual regulation of MET expression Proc. Natl. Acad. Sci. U. S. A., 108 (2011),pp. 14240-14245
[8]	Jin, K., Xiang, Y., Tang, J. et al. miR-34 is associated with poor prognosis of patients with gallbladder cancer through regulating telomere length in tumor stem cells Tumour Biol., 35 (2014),pp. 1503-1510
[9]	Kim, Y.H., Lee, W.K., Lee, E.B. et al. Combined effect of metastasis-related microRNA, miR-34 and miR-124 family, methylation on prognosis of non-small-cell lung cancer Clin. Lung Cancer, 18 (2017),pp. e13-e20
[10]	Lisowska, K.M., Olbryt, M., Dudaladava, V. et al. Gene expression analysis in ovarian cancer - faults and hints from DNA microarray study Front. Oncol, 4 (2014),p. 6
[11]	Mateescu, B., Batista, L., Cardon, M. et al. miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response Nat. Med., 17 (2011),pp. 1627-1635
[12]	Misso, G., Di Martino, M.T., De Rosa, G. et al. Mir-34: a new weapon against cancer? Mol. Ther. Nucleic Acids, 3 (2014),p. e194
[13]	Mok, S.C., Bonome, T., Vathipadiekal, V. et al. A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2 Cancer Cell, 16 (2009),pp. 521-532
[14]	Peng, W.X., Koirala, P., Mo, Y.Y. LncRNA-mediated regulation of cell signaling in cancer Oncogene, 36 (2017),pp. 5661-5667
[15]	Rajendiran, S., Parwani, A.V., Hare, R.J. et al. MicroRNA-940 suppresses prostate cancer migration and invasion by regulating MIEN1 Mol. Cancer, 13 (2014),p. 250
[16]	Rokavec, M., Li, H., Jiang, L. et al. The p53/miR-34 axis in development and disease J. Mol. Cell Biol., 6 (2014),pp. 214-230
[17]	Rupaimoole, R., Slack, F.J. A role for miR-34 in colon cancer stem cell homeostasis Stem Cell Investig., 3 (2016),p. 42
[18]	Schmid, G., Notaro, S., Reimer, D. et al. Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer BMC Cancer, 16 (2016),p. 102
[19]	Tothill, R.W., Tinker, A.V., George, J. et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome Clin. Cancer Res., 14 (2008),pp. 5198-5208
[20]	Vogt, M., Munding, J., Gruner, M. et al. Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas Virchows Arch., 458 (2011),pp. 313-322
[21]	Webb, P.M., Jordan, S.J. Epidemiology of epithelial ovarian cancer Best Pract. Res. Clin. Obstet. Gynaecol., 41 (2017),pp. 3-14
[22]	Wong, K.Y., Yu, L., Chim, C.S. DNA methylation of tumor suppressor miRNA genes: a lesson from the miR-34 family Epigenomics, 3 (2011),pp. 83-92
[23]	Yamakuchi, M., Lowenstein, C.J. MiR-34, SIRT1 and p53: the feedback loop Cell Cycle, 8 (2009),pp. 712-715
[24]	Yang, Y., Jiang, Y., Wan, Y. et al. UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis Tumour Biol., 37 (2016),pp. 10633-10641
[25]	Yuan, J.M., Shi, X.J., Sun, P. et al. Downregulation of cell cycle-related proteins in ovarian cancer line and cell cycle arrest induced by microRNA Int. J. Clin. Exp. Med., 8 (2015),pp. 18476-18481
[26]	Zhang, Z., Cheng, J., Wu, Y. et al. LncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian cancer Mol. Med. Rep., 14 (2016),pp. 2465-2472
[27]	Zhang, Z., Zhang, B., Li, W. et al. Epigenetic silencing of miR-203 upregulates SNAI2 and contributes to the invasiveness of malignant breast cancer cells Genes Cancer, 2 (2011),pp. 782-791