Decreased miR-452 expression in human cervical cancer and its prognostic significance

Objective: MicroRNA-452 (miR 452) was previously reported to be dysregulated in several types of human cancers and involved in tumor progression. However, its role in cervical cancer is still unclear. The aim of this study was to investigate the clinical significance and prognostic value of miR-452 expression in human cervical cancer. Materials and Methods: The expressions of miR-452 was detected in 137 pairs of cervical cancer specimens and adjacent non-cancerous tissues using qRT PCR assay. Then, the association of miR 452 levels with clinicopathological features and prognosis was evaluated. Results: MiR-452 expression was significantly downregulated in cervical cancer tissues than those corresponding non-cancerous tissues (p < 0.001). Decreased miR-452 expression was linked to lymph node metastasis, vascular invasion, poor tumor differentiation, advanced FIGO Stage, and short overall survival. Multivariate Cox regression analysis confirmed that low level of miR-452 expression predicted poor prognosis of patients with cervical cancer independently. Conclusions: The present results suggest that miR-452 downregulation may be involved in cervical cancer formation and progression, and that miR-452 would serve as a novel prognostic biomarker for patients with this disease.

MicroRNA-452; Cervical cancer; Real-time quantitative RT-PCR; Prognosis.

[1] Siegel R., Naishadham D., Jemal A.: “Cancer statistics, 2012”. CA Cancer J Clin., 2012, 62, 10.

[2] Arbyn M., Castellsague X., de Sanjose S., Bruni L., Saraiya M., Bray F., et al.: Worldwide burden of cervical cancer in 2008”. Ann. Oncol., 2011, 22, 2675.

[3] Hildesheim A., Wang S.S.: “Host and viral genetics and risk of cervical cancer: a review”. Virus Res., 2002, 89, 229.

[4] Bartel D.P.: “MicroRNAs: genomics, biogenesis, mechanism, and function”. Cell, 2004, 116, 281.

[5] Adams B.D., Kasinski A.L.; Slack F.J.: “Aberrant regulation and function of microRNAs in cancer”. Curr. Biol., 2014, 24, R762.

[6] Bueno M.J., Perez de Castro I., Malumbres M.: “Control of cell proliferation pathways by microRNAs” Cell Cycle, 2008, 7, 3143.

[7] Nicoloso M.S., Spizzo R., Shimizu M., Rossi S., Calin G.A.: “MicroRNAs— the micro steering wheel of tumour metastases”. Nat. Rev. Cancer, 2009, 9, 293.

[8] Zaravinos A.: “The Regulatory Role of MicroRNAs in EMT and Cancer”. J. Oncol., 2015, 2015, 865816.

[9] Wang W., Zhang E., Lin C.: “MicroRNAs in tumor angiogenesis” Life Sci., 2015, 136, 28.

[10] Guo Z., Shu Y., Zhou H., Zhang W.: “Identification of diagnostic and prognostic biomarkers for cancer: Focusing on genetic variations in microRNA regulatory pathways (Review)”. Mol Med Rep., 2016, 13, 1943.

[11] Yang Y., Song K.L., Chang H.. Chen L.: “Decreased expression of microRNA-126 is associated with poor prognosis in patients with cervical cancer”. Diagn. Pathol., 2014, 9, 220.

[12] Yin Z.L., Wang Y.L., Ge S.F., Guo T.T., Wang L., Zheng X.M., et al.: “Reduced expression of miR-503 is associated with poor prognosis in cervical cancer”. Eur. Rev. Med. Pharmacol. Sci., 2015, 19, 4081.

[13] Luo M., Shen D., Wang W., Xian J.: “Aberrant expression of microRNA- 26b and its prognostic potential in human cervical cancer” Int. J. Clin. Exp. Pathol., 2015, 8, 5542.

[14] You W., Wang Y., Zheng J.: “Plasma miR-127 and miR-218 might serve as potential biomarkers for cervical cancer” Reprod. Sci., 2015, 22, 1037.

[15] Song X., Shi B., Huang K., Zhang W.: “miR-133a inhibits cervical cancer growth by targeting EGFR”. Oncol. Rep., 2015, 34, 1573.

[16] Tang Y., Wang Y., Chen Q., Qiu N., Zhao Y.; You X.: MiR-223 inhibited cell metastasis of human cervical cancer by modulating epithelial- mesenchymal transition”. Int. J. Clin. Exp. Pathol., 2015, 8, 11224.

[17] Liu S., Song L., Zhang L., Zeng S., Gao F.: “miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1”. Biochem. Biophys. Res. Commun., 2015,

459, 679.

[18] Yu Q., Liu S.L., Wang H., Shi G., Yang P., Chen X.L.: “miR-126 Suppresses the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin”. Asian Pac. J. Cancer Prev., 2014, 14, 6569.

[19] Liu L., Chen K., Wu J., Shi L., Hu B., Cheng S., et al.: “Downregulation of miR-452 promotes stem-like traits and tumorigenicity of gliomas”. Clin. Cancer Res., 2013, 19, 3429.

[20] He Z., Xia Y., Pan C., Ma T., Liu B., Wang J., I: “Up-Regulation of MiR-452 Inhibits Metastasis of Non-Small Cell Lung Cancer by Regulating BMI1”. Cell Physiol. Biochem., 2015, 37, 387.

[21] Puerta-Gil P., Garcia-Baquero R., Jia A. Y., Ocana S., Alvarez-Mugica M., Alvarez-Ossorio J.L., et al.: “miR-143, miR-222, and miR- 452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer” Am. J. Pathol., 2012, 180, 1808.

[22] Kristensen H., Haldrup C., Strand S., Mundbjerg K., Mortensen M. M., Thorsen K., et al.: “Hypermethylation of the GABRE~miR- 452~miR-224 promoter in prostate cancer predicts biochemical recurrence after radical prostatectomy”. Clin. Cancer Res., 2014, 20,

2169.

[23] Veerla S., Lindgren D., Kvist A., Frigyesi A., Staaf J., Persson H., et