Top

Published in:

01-04-2020 | Glioma | Original Article

Effects of microRNA-195 on the Prognosis of Glioma Patients and the Proliferation and Apoptosis of Human Glioma Cells

Authors: Ying Jia, Ye Tian, Shuo An, Dong Yang

Published in: Pathology & Oncology Research | Issue 2/2020

Abstract

Glioma is the most common and aggressive intracranial malignant tumor with poor prognosis. Acts as a tumor suppressor, microRNA-195 (miR-195) plays important roles in a variety of cancers. However, the expression of miR-195 and role of miR-195 in glioma are still not well understood. 186 patients with glioma were enrolled and the follow-up period ranges from 1 to 69 months. MiR-195 was exogenously transfected into human glioma U87 cell line. The cell proliferation assay (CCK-8), colony formation assay, cell cycle analysis and cell apoptosis analysis were examined to investigate miR-195 effect on U87 cells. MiR-195 levels were reversely correlated with pathological grades (r = −0.487, p = 0.003). For patients with low miR-195 levels, their median survival time was 15 months, whereas the median survival time in patients with high miR-195 levels was 56.53 months. Multi-factor Cox regression analysis showed that high level of miR-195 (Odds ratio (OR): 0.347, 95% CI: 0.121–0.992) was associated with decreased mortality risk of patients. Moreover, overexpression of miR-195 inhibits proliferation and colony formation, and induces apoptosis of U87 cells. MiR-195 could block the glioma cells in G0/G1 phase, reducing S phase cells and regulating apoptosis related proteins (Caspase-3, Caspase-8, Caspase-9 and Bcl-2). Downregulation of miR-195 was associated with poor prognosis in human glioma. MiR-195 acted as tumor suppressor through inhibiting cell proliferation and promoting cell apoptosis via blockade of cell cycle and regulation of apoptosis related proteins.

Li K, Lu D, Guo Y, Wang C, Liu X, Liu Y, Liu D (2018) Trends and patterns of incidence of diffuse glioma in adults in the United States, 1973-2014. Cancer Med 7:5281–5290. https://doi.org/10.1002/cam4.1757 CrossRefPubMedPubMedCentral

Xia Z, Qiu D, Deng J, Jiao X, Yang R, Sun Z, Wan X, Li J (2018) Methylation-induced downregulation and tumor-suppressive role of microRNA-98 in glioma through targeting Sal-like protein 4. Int J Mol Med 41(5):2651–2659. https://doi.org/10.3892/ijmm.2018.3464 CrossRefPubMedPubMedCentral

Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442 CrossRefPubMed

Ahir BK, Ozer H, Engelhard HH, Lakka SS (2017) MicroRNAs in glioblastoma pathogenesis and therapy: a comprehensive review. Crit Rev Oncol Hematol 120:22–33. https://doi.org/10.1016/j.critrevonc.2017.10.003 CrossRefPubMed

Barciszewska AM (2016) MicroRNAs as efficient biomarkers in high-grade gliomas. Folia Neuropathol 54(4):369–374. https://doi.org/10.5114/fn.2016.64812 CrossRefPubMed

Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297CrossRefPubMed

Zhang F, Meng W, Tong B (2016) Down-regulation of MicroRNA-133b suppresses apoptosis of Lens epithelial cell by up-regulating BCL2L2 in age-related cataracts. Med Sci Monit 22:4139–4145CrossRefPubMedPubMedCentral

Zhang Y, Peng Z, Zhao Y, Chen L (2016) microRNA-25 inhibits cell apoptosis of human gastric adenocarcinoma cell line AGS via regulating CCNE1 and MYC. Med Sci Monit 22:1415–1420CrossRefPubMedPubMedCentral

Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ (2010) Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 251(3):499–505. https://doi.org/10.1097/SLA.0b013e3181cc939f CrossRefPubMed

10.

Chen H, Untiveros GM, McKee LA, Perez J, Li J, Antin PB, Konhilas JP (2012) Micro-RNA-195 and -451 regulate the LKB1/AMPK signaling axis by targeting MO25. PLoS One 7(7):e41574. https://doi.org/10.1371/journal.pone.0041574 CrossRefPubMedPubMedCentral

11.

Busk PK, Cirera S (2010) MicroRNA profiling in early hypertrophic growth of the left ventricle in rats. Biochem Biophys Res Commun 396(4):989–993. https://doi.org/10.1016/j.bbrc.2010.05.039 CrossRefPubMed

12.

Joglekar MV, Parekh VS, Mehta S, Bhonde RR, Hardikar AA (2007) MicroRNA profiling of developing and regenerating pancreas reveal post-transcriptional regulation of neurogenin3. Dev Biol 311(2):603–612. https://doi.org/10.1016/j.ydbio.2007.09.008 CrossRefPubMed

13.

Yu S, Jing L, Yin XR, Wang MC, Chen YM, Guo Y, Nan KJ, Han LL (2017) MiR-195 suppresses the metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by inhibiting YAP. Oncotarget 8(59):99757–99771. https://doi.org/10.18632/oncotarget.20909 CrossRefPubMedPubMedCentral

14.

Jia LF, Wei SB, Gong K, Gan YH, Yu GY (2013) Prognostic implications of micoRNA miR-195 expression in human tongue squamous cell carcinoma. PLoS One 8(2):e56634. https://doi.org/10.1371/journal.pone.0056634 CrossRefPubMedPubMedCentral

15.

Cecene G, Ak S, Eskiler GG, Demirdogen E, Erturk E, Gokgoz S, Polatkan V, Egeli U, Tunca B, Tezcan G, Topal U, Tolunay S, Tasdelen I (2016) Circulating miR-195 as a therapeutic biomarker in Turkish breast Cancer patients. Asian Pac J Cancer Prev 17(9):4241–4246PubMed

16.

Soon PS, Tacon LJ, Gill AJ, Bambach CP, Sywak MS, Campbell PR, Yeh MW, Wong SG, Clifton-Bligh RJ, Robinson BG, Sidhu SB (2009) miR-195 and miR-483-5p identified as predictors of poor prognosis in adrenocortical Cancer. Clin Cancer Res 15(24):7684–7692. https://doi.org/10.1158/1078-0432.CCR-09-1587 CrossRefPubMed

17.

Wang R, Zhao N, Li S, Fang JH, Chen MX, Yang J, Jia WH, Yuan Y, Zhuang SM (2013) MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42. Hepatology 58(2):642–653. https://doi.org/10.1002/hep.26373 CrossRefPubMed

18.

Lakomy R, Sana J, Hankeova S, Fadrus P, Kren L, Lzicarova E, Svoboda M, Dolezelova H, Smrcka M, Vyzula R, Michalek J, Hajduch M, Slaby O (2011) MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients. Cancer Sci 102(12):2186–2190. https://doi.org/10.1111/j.1349-7006.2011.02092.x CrossRefPubMed

19.

Ilhan-Mutlu A, Wohrer A, Berghoff AS, Widhalm G, Marosi C, Wagner L, Preusser M (2013) Comparison of microRNA expression levels between initial and recurrent glioblastoma specimens. J Neuro-Oncol 112(3):347–354. https://doi.org/10.1007/s11060-013-1078-6 CrossRef

20.

Zhang QQ, Xu H, Huang MB, Ma LM, Huang QJ, Yao Q, Zhou H, Qu LH (2012) MicroRNA-195 plays a tumor-suppressor role in human glioblastoma cells by targeting signaling pathways involved in cellular proliferation and invasion. Neuro-Oncology 14(3):278–287. https://doi.org/10.1093/neuonc/nor216 CrossRefPubMedPubMedCentral

21.

Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, Ambros VR, Israel MA (2007) Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res 67(6):2456–2468. https://doi.org/10.1158/0008-5472.CAN-06-2698 CrossRefPubMed

22.

Henriksen M, Johnsen KB, Olesen P, Pilgaard L, Duroux M (2014) MicroRNA expression signatures and their correlation with clinicopathological features in glioblastoma multiforme. NeuroMolecular Med 16(3):565–577. https://doi.org/10.1007/s12017-014-8309-7 CrossRefPubMed

23.

Wang A, Ren M, Song Y, Wang X, Wang Q, Yang Q, Liu H, Du Z, Zhang G, Wang J (2018) MicroRNA expression profiling of bone marrow mesenchymal stem cells in steroid-induced osteonecrosis of the femoral head associated with osteogenesis. Med Sci Monit 24:1813–1825CrossRefPubMedPubMedCentral

24.

Liu L, Chen L, Xu Y, Li R, Du X (2010) microRNA-195 promotes apoptosis and suppresses tumorigenicity of human colorectal cancer cells. Biochem Biophys Res Commun 400(2):236–240. https://doi.org/10.1016/j.bbrc.2010.08.046 CrossRefPubMed

25.

Li C, Zhao Q, Zhang W, Chen M, Ju W, Wu L, Han M, Ma Y, Zhu X, Wang D, Guo Z, He X (2017) MicroRNA-146b-5p identified in porcine liver donation model is associated with early allograft dysfunction in human liver transplantation. Med Sci Monit 23:5876–5884CrossRefPubMedPubMedCentral

26.

Yu M, Zhang X, Li H, Zhang P, Dong W (2017) MicroRNA-588 is downregulated and may have prognostic and functional roles in human breast cancer. Med Sci Monit 23:5690–5696CrossRefPubMedPubMedCentral

27.

Li F, Liang A, Lv Y, Liu G, Jiang A, Liu P (2017) MicroRNA-200c inhibits epithelial-mesenchymal transition by targeting the BMI-1 gene through the Phospho-AKT pathway in endometrial carcinoma cells in vitro. Med Sci Monit 23:5139–5149CrossRefPubMedPubMedCentral

28.

Tian Z, Zhou H, Xu Y, Bai J (2017) MicroRNA-495 inhibits new bone regeneration via targeting high mobility group AT-hook 2 (HMGA2). Med Sci Monit 23:4689–4698CrossRefPubMedPubMedCentral

29.

Zhang Z, Li H, Chen S, Li Y, Cui Z, Ma J (2017) Knockdown of MicroRNA-122 protects H9c2 cardiomyocytes from hypoxia-induced apoptosis and promotes autophagy. Med Sci Monit 23:4284–4290CrossRefPubMedPubMedCentral

30.

Fang DZ, Wang YP, Liu J, Hui XB, Wang XD, Chen X, Liu D (2018) MicroRNA-129-3p suppresses tumor growth by targeting E2F5 in glioblastoma. Eur Rev Med Pharmacol Sci 22(4):1044–1050. https://doi.org/10.26355/eurrev_201802_14387 CrossRefPubMed

31.

Szemraj M, Oszajca K, Szemraj J, Jurowski P (2017) MicroRNA expression analysis in serum of patients with congenital hemochromatosis and age-related macular degeneration (AMD). Med Sci Monit 23:4050–4060CrossRefPubMedPubMedCentral

32.

Zhang J, Qin L, Han L, Zhao Y, Jing H, Song W, Shi H (2017) Role of MicroRNA-93 I in pathogenesis of left ventricular remodeling via targeting cyclin-D1. Med Sci Monit 23:3981–3988CrossRefPubMedPubMedCentral

33.

Gan TQ, Chen WJ, Qin H, Huang SN, Yang LH, Fang YY, Pan LJ, Li ZY, Chen G (2017) Clinical value and prospective pathway signaling of MicroRNA-375 in lung adenocarcinoma: a study based on the Cancer genome atlas (TCGA), gene expression omnibus (GEO) and bioinformatics analysis. Med Sci Monit 23:2453–2464CrossRefPubMedPubMedCentral

Title: Effects of microRNA-195 on the Prognosis of Glioma Patients and the Proliferation and Apoptosis of Human Glioma Cells
Authors: Ying Jia
Ye Tian
Shuo An
Dong Yang
Publication date: 01-04-2020
Publisher: Springer Netherlands
Keywords: Glioma
Glioma
Glioma
Published in: Pathology & Oncology Research / Issue 2/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-019-00622-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2020

Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma

Silencing UHRF1 Inhibits Cell Proliferation and Promotes Cell Apoptosis in Retinoblastoma Via the PI3K/Akt Signalling Pathway

The Association of Androgen Receptor Expression with Renal Cell Carcinoma Risk: a Systematic Review and Meta-Analysis

CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition

Association between Genetic Polymorphisms in microRNA Machinery Genes and Risk of Papillary Thyroid Carcinoma

Acute and Late Toxicity after Moderate Hypofractionation with Simultaneous Integrated Boost (SIB) Radiation Therapy for Prostate Cancer. A Single Institution, Prospective Study

Keynote webinar | Spotlight on antibody–drug conjugates in cancer