Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

  • Li, Ping (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Xie, Xiao-Bing (Medical Laboratory Center, First Affiliated Hospital, Hunan University of Chinese Medicine) ;
  • Chen, Qian (Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine) ;
  • Pang, Guo-Lian (Department of Pathology, First People Hospital of Qujing) ;
  • Luo, Wan (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Tu, Jian-Cheng (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Zheng, Fang (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Liu, Song-Mei (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Han, Lu (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Zhang, Jian-Kun (Department of Pathology, First People Hospital of Qujing) ;
  • Luo, Xian-Yong (Department of Pathology, First People Hospital of Qujing) ;
  • Zhou, Xin (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University)
  • Published : 2014.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

Keywords

References

  1. Ambros V (2001). MicroRNAs: tiny regulators with great potential. Cell, 107, 823-6. https://doi.org/10.1016/S0092-8674(01)00616-X
  2. Bartel DP (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116, 281-97. https://doi.org/10.1016/S0092-8674(04)00045-5
  3. Cai CK, Zhao GY, Tian LY, et al (2012). miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncol Rep, 28, 1764-70.
  4. Chen C, Ridzon DA, Broomer AJ, et al (2005). Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res, 33, 179. https://doi.org/10.1093/nar/gni178
  5. Chen Q, Xia HW, Ge XJ, et al (2013). Serum miR-19a predicts resistance to FOLFOX chemotherapy in advanced colorectal cancer cases. Asian Pac J Cancer Prev, 14, 7421-6. https://doi.org/10.7314/APJCP.2013.14.12.7421
  6. Cortez MA, Welsh JW, Calin GA (2012). Circulating microRNAs as noninvasive biomarkers in breast cancer. Recent Results Cancer Res, 195, 151-61. https://doi.org/10.1007/978-3-642-28160-0_13
  7. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  8. Garzon R, Heaphy CE, Havelange V, et al (2009). MicroRNA 29b functions in acute myeloid leukemia. Blood, 114, 5331-41. https://doi.org/10.1182/blood-2009-03-211938
  9. Guo J, Shou C, Meng L, et al (2007). Neuronal protein synuclein gamma predicts poor clinical outcome in breast cancer. Int J Cancer, 121, 1296-305. https://doi.org/10.1002/ijc.22763
  10. Harquail J, Benzina S, Robichaud GA (2012). MicroRNAs and breast cancer malignancy: an overview of miRNA-regulated cancer processes leading to metastasis. Cancer Epidemiol Biomarkers Prev, 11, 269-80.
  11. Huang F, Liu C, Shi YH, et al (2013). MicroRNA-101 inhibits cell proliferation, invasion, and promotes apoptosis by regulating cyclooxygenase-2 in Hela cervical carcinoma cells. Asian Pac J Cancer Prev, 14, 5915-20. https://doi.org/10.7314/APJCP.2013.14.10.5915
  12. Jiang Y, Liu YE, Goldberg ID, et al (2004). A novel heat-shock protein-associated chaperone, stimulates ligand-dependent estrogen receptor $\alpha$ signaling and mammary tumorigenesis. Cancer Res, 64, 4539-46. https://doi.org/10.1158/0008-5472.CAN-03-3650
  13. Jiang Y, Liu YE, Lu A, et al (2003). Stimulation of estrogen receptor signaling by gamma synuclein. Cancer Res, 63, 3899-903.
  14. Lian J, Zhang X, Tian H, et al (2009). Altered microRNA expression in patients with non-obstructive zoospermia. Reprod Biol Endocrinol, 7, 13. https://doi.org/10.1186/1477-7827-7-13
  15. Liu YE, Pu W, Jiang Y, et al (2007). Chaperoning of estrogen receptor and induction of mammary gland proliferation by neuronal protein synuclein gamma. Oncogene, 26, 2115-25. https://doi.org/10.1038/sj.onc.1210000
  16. Luo Q, Li X, Li J, et al (2013). MiR-15a is underexpressed and inhibits the cell cycle by targeting CCNE1 in breast cancer. Int J Oncol, 43, 1212-8.
  17. Ng SB, Yan J, Huang G, et al (2011). Dysregulated microRNAs affect pathways and targets of biologic relevance in nasaltype natural killer/T-cell lymphoma. Blood, 118, 4919-29. https://doi.org/10.1182/blood-2011-07-364224
  18. Paik JH, Jang JY, Jeon YK, et al (2011). MicroRNA-146a Downregulates $NF{\kappa}B$ Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma. Clin Cancer Res, 17, 4761-71. https://doi.org/10.1158/1078-0432.CCR-11-0494
  19. Qin XJ, Ling BX (2012). Proteomic studies in breast cancer (Review). Oncol Lett, 3, 735-43.
  20. Shenouda SK, Alahari SK (2009). MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev, 28, 369-78. https://doi.org/10.1007/s10555-009-9188-5
  21. Thorsen SB, Obad S, Jensen NF, et al (2012). The therapeutic potential of microRNAs in cancer. Cancer J, 18, 275-84. https://doi.org/10.1097/PPO.0b013e318258b5d6
  22. Valencia-Sanchez MA, Liu J, Hannon GJ, et al (2006). Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev, 20, 515-24. https://doi.org/10.1101/gad.1399806
  23. Wang H, Tan G, Dong L, et al (2012). Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One, 7, 34210. https://doi.org/10.1371/journal.pone.0034210
  24. Wei F, Xu J, Tang L, et al (2012). p27 (Kip1) V109G polymorphism and cancer risk: a systematic review and meta-analysis. Cancer Biother Radiopharm, 27, 665-71.
  25. Wu K, Quan Z, Weng Z, et al (2007). Expression of neuronal protein synuclein gamma gene as a novel marker for breast cancer prognosis. Breast Cancer Res Treatment, 101, 259-67. https://doi.org/10.1007/s10549-006-9296-7
  26. Yamanaka Y, Tagawa H, Takahashi N, et al (2009). Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia. Blood, 114, 3265-75. https://doi.org/10.1182/blood-2009-06-222794
  27. Yu Q, Liu SL, Wang H, et al (2013). miR-126 Suppresses the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin. Asian Pac J Cancer Prev, 14, 6569-72. https://doi.org/10.7314/APJCP.2013.14.11.6569

Cited by

  1. MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression vol.36, pp.3, 2015, https://doi.org/10.1007/s13277-014-2794-z
  2. miR-365 overexpression promotes cell proliferation and invasion by targeting ADAMTS-1 in breast cancer vol.47, pp.1, 2015, https://doi.org/10.3892/ijo.2015.3015
  3. Downregulation of microRNA-497 is associated with upregulation of synuclein γ in patients with osteosarcoma vol.12, pp.6, 2016, https://doi.org/10.3892/etm.2016.3838
  4. MicroRNA-15a inhibits the growth and invasiveness of malignant melanoma and directly targets on CDCA4 gene vol.37, pp.10, 2016, https://doi.org/10.1007/s13277-016-5271-z
  5. Circulating long noncoding RNA GAS5 as a potential biomarker in breast cancer for assessing the surgical effects vol.37, pp.5, 2016, https://doi.org/10.1007/s13277-015-4568-7
  6. miR-15a-5p acts as an oncogene in renal cell carcinoma vol.15, pp.3, 2017, https://doi.org/10.3892/mmr.2017.6121
  7. MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway vol.7, pp.2045-2322, 2017, https://doi.org/10.1038/srep41942
  8. Downregulation of microRNA-15a suppresses the proliferation and invasion of renal cell carcinoma via direct targeting of eIF4E vol.38, pp.4, 2017, https://doi.org/10.3892/or.2017.5901