Asian Journal of Pharmaceutical Research and Health Care

Open Access Open Access  Restricted Access Subscription Access

Study of Mir-141 and its Potential Targeted mRNA PTEN Expression in Nasopharyngeal Carcinoma:From in Silico to Initial Experiment Analysis


Affiliations
1 University of Science, Vietnam National University Ho Chi Minh City, Viet Nam
2 Ho Chi Minh City Open University, Ho Chi Minh City, Viet Nam
 

Recently, accumulating evidences indicated that microRNA-141 (miR-141) is associated with NPC due to their abilities to affect the expression of genes that modulate tumorigenesis. Unfortunately, there is still limited publication about miR-141 expression in Vietnamese nasopharyngeal cancer patients. In this study, we adopted bioinformatics tools, such as Pictar, Target Scan, miRDB, etc. to predict its target gene. As the results, PTEN (phosphatase and tensin homolog gene), acts oncogenic role associated with biological processes lead to the nasopharyngeal carcinogenesis, was identified as the direct target of miR-141. Experimentally, we reported the evaluation of miR-141 and PTEN expression in NPC biopsy samples and non-cancerous swab samples. The present study demonstrated that miR-141 was upregulated 9.38 times, and PTEN expression was significantly lowered in NPC biopsy samples compared to non-cancerous epithelial swab samples. Our finding demonstrated that the miR-141 was upregulated and PTEN was down regulated in NPC biopsy samples. In the upcoming research, a larger clinical sample size from patients at each stage of the NPC will be performed to understand the expression pattern of the miR-141 and PTEN for further applied in early diagnosis and prognosis as well as therapeutic of NPC.

Keywords

miR-141, Nasopharyngeal Carcinoma, PTEN.
User
Notifications
Font Size

  • GLOBOCAN. Estimated cancer incidence, mortality and prevalence worldwide in 2012; 2012. Available from: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx

  • Mahdavifar N, Ghoncheh M, Mohammadian-Hafshejani A, Khosravi B, Salehiniya H. Epidemiology and inequality in the incidence and mortality of Nasopharynx cancer in Asia. Osong Public Health and Research Perspectives. 2016; 7(6):360–72. https://doi.org/10.1016/j.phrp.2016.11.002 PMid:28053841 PMCid:PMC5194228

  • Croce CM, Calin GA. miRNAs, cancer, and stem cell division. Cell. 2005; 122(1):6–7. https://doi.org/10.1016/j.cell.2005.06.036 PMid:16009126

  • Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell. 2009; 136(2):215–33. https://doi.org/10.1016/j.cell.2009.01.002 PMid:19167326 PMCid:PMC3794896

  • He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522–31. https://doi.org/10.1038/nrg1379 PMid:15211354

  • Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol. 2007; 23:175–205. https://doi.org/10.1146/ annurev.cellbio.23.090506.123406 PMid:17506695

  • Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857–66. https://doi.org/10.1038/nrc1997 PMid:17060945

  • Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014; 15(8):509–24. https://doi.org/10.1038/nrm3838 PMid:25027649

  • Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007; 302(1):1–12. https://doi.org/10.1016/j.ydbio.2006.08.028

  • Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med. 2014; 20(8):460-9. https://doi.org/10.1016/j.molmed.2014.06.005 PMid:25027972

  • Kala R, Peek GW, Hardy TM, Tollefsbol TO. MicroRNAs: an emerging science in cancer epigenetics. J Clin Bioinforma. 2013; 3(1):6. https://doi.org/10.1186/2043-9113-3-6 PMid:23497588 PMCid:PMC3608239

  • Lee KT, Tan JK, Lam AK, Gan SY. MicroRNAs serving as potential biomarkers and therapeutic targets in nasopharyngeal carcinoma: A critical review. Crit Rev Oncol Hematol. 2016; 103:1–9. https://doi.org/10.1016/j.critrevonc.2016.04.006 PMid:27179594

  • Zhang L, Deng T, Li X, Liu H, Zhou H, Ma J, et al. microRNA-141 is involved in a nasopharyngeal carcinomarelated genes network. Carcinogenesis. 2010; 31(4):559–66. https://doi.org/10.1093/carcin/bgp335 PMid:20053927

  • Zuo QF, Zhang R, Li BS, Zhao YL, Zhuang Y, Yu T, et al. MicroRNA-141 inhibits tumor growth and metastasis in gastric cancer by directly targeting transcriptional co-activator with PDZ-binding motif, TAZ. Cell Death Dis. 2015; 6:e1623. https://doi.org/10.1038/cddis.2014.573

  • Liu Y, Zhao R, Wang H, Luo Y, Wang X, Niu W, et al. miR-141 is involved in BRD7-mediated cell proliferation and tumor formation through suppression of the PTEN/ AKT pathway in nasopharyngeal carcinoma. Cell Death Dis. 2016; 7:e2156. https://doi.org/10.1038/cddis.2016.64 PMid:27010857 PMCid:PMC4823963

  • Liu Y, Zhao R, Wei Y, Li M, Wang H, Niu W, et al. BRD7 expression and c-Myc activation forms a double-negative feedback loop that controls the cell proliferation and tumor growth of nasopharyngeal carcinoma by targeting oncogenic miR-141. J Exp Clin Cancer Res. 2018; 37(1):64. https://doi.org/10.1186/s13046-018-0734-2 PMid:29559001 PMCid:PMC5859396

  • Lao DT, Truong KP, Le HAT. miRNA-141 as the Biomarker for Human Cancers. AJPRHC. 2018; 10(2):42-9. https:// doi.org/10.18311/ajprhc/2018/21486

  • Sano T, Lin H, Chen X, Langford LA, Koul D, Bondy ML, et al. Differential expression of MMAC/PTEN in glioblastoma multiforme: relationship to localization and prognosis. Cancer Res. 1999; 59(8):1820–4. PMid:10213484

  • Li A, Zhang XS, Jiang JH, Wang HH, Liu XQ, Pan ZG, et al. Transcriptional expression of RPMS1 in nasopharyngeal carcinoma and its oncogenic potential. Cell Cycle. 2005; 4(2):304–9. https://doi.org/10.4161/cc.4.2.1416 PMid:15725729

  • Sun H, Lesche R, Li DM, Liliental J, Zhang H, Gao J, et al. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc Natl Acad Sci U S A. 1999; 96(11):6199–204. https://doi.org/10.1073/ pnas.96.11.6199 PMid:10339565 PMCid:PMC26859

  • Mahimainathan L, Choudhury GG. Inactivation of plateletderived growth factor receptor by the tumor suppressor PTEN provides a novel mechanism of action of the phosphatase. J Biol Chem. 2004; 279(15):15258–68. https:// doi.org/10.1074/jbc.M314328200 PMid:14718524

  • Shinde SR, Maddika S. PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7. Nat Commun. 2016; 7:10689. https://doi.org/10.1038/ ncomms10689 PMid:26869029 PMCid:PMC4754336

  • Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov. 2016; 6(2):202–16. https:// doi.org/10.1158/2159-8290.CD-15-0283 PMid:26645196 PMCid:PMC4744499

  • Hill R, Wu H. PTEN, stem cells, and cancer stem cells. J Biol Chem. 2009; 284(18):11755–9. https://doi.org/10.1074/jbc.R800071200 PMid:19117948 PMCid:PMC2673242

  • Maier D, Jones G, Li X, Schönthal AH, Gratzl O, Van Meir EG, et al. The PTEN lipid phosphatase domain is not required to inhibit invasion of glioma cells. Cancer Res. 1999; 59(21):5479–82. PMid:10554022

  • Leslie NR, Yang X, Downes CP, Weijer CJ. PtdIns(3,4,5) P(3)-dependent and -independent roles for PTEN in the control of cell migration. Curr Biol. 2007; 17(2):115–25. https://doi.org/10.1016/j.cub.2006.12.026 PMid:17240336 PMCid:PMC1885949

  • Puc J, Parsons R. PTEN loss inhibits CHK1 to cause double stranded-DNA breaks in cells. Cell Cycle. 2005; 4(7):927–9. https://doi.org/10.4161/cc.4.7.1795 PMid:15970699

  • Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007; 128(1):157–70. https:// doi.org/10.1016/j.cell.2006.11.042 PMid:17218262

  • Li J, Simpson L, Takahashi M, Miliaresis C, Myers MP, Tonks N, et al. The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene. Cancer Res. 1998; 58(24):5667–72. PMid:9865719

  • Xu Z, Stokoe D, Kane LP, Weiss A. The inducible expression of the tumor suppressor gene PTEN promotes apoptosis and decreases cell size by inhibiting the PI3K/Akt pathway in Jurkat T cells. Cell Growth Differ. 2002; 13(7):285–96. PMid:12133897

  • Pal A, Barber TM, Van de Bunt M, Rudge SA, Zhang Q, Lachlan KL, et al. PTEN mutations as a cause of constitutive insulin sensitivity and obesity. N Engl J Med. 2012; 367(11):1002–11. https://doi.org/10.1056/ NEJMoa1113966 PMid:22970944 PMCid:PMC4072504

  • Ortega-Molina A, Serrano M. PTEN in cancer, metabolism, and aging. Trends Endocrinol Metab. 2013; 24(4):184–9. https://doi.org/10.1016/j.tem.2012.11.002 PMid:23245767 PMCid:PMC3836169

  • Markopoulos GS, Roupakia E, Tokamani M, Chavdoula E, Hatziapostolou M, Polytarchou C, et al. A step-by-step microRNA guide to cancer development and metastasis. Cell Oncol (Dordr). 2017; 40(4):303–39. https://doi.org/10.1007/s13402-017-0341-9 PMid:28748501

  • Chen P, Guo X, Zhou H, Zhang W, Zeng Z, Liao Q, et al. SPLUNC1 regulates cell progression and apoptosis through the miR-141-PTEN/p27 Pathway, but is hindered by LMP1. Samant R, editor. PLoS ONE. 2013; 8(3):e56929.


Abstract Views: 360

PDF Views: 188




  • Study of Mir-141 and its Potential Targeted mRNA PTEN Expression in Nasopharyngeal Carcinoma:From in Silico to Initial Experiment Analysis

Abstract Views: 360  |  PDF Views: 188

Authors

Duc Thuan Lao
University of Science, Vietnam National University Ho Chi Minh City, Viet Nam
Danh Hoang Nguyen
Ho Chi Minh City Open University, Ho Chi Minh City, Viet Nam
Thuy Ai Huyen Le
Ho Chi Minh City Open University, Ho Chi Minh City, Viet Nam

Abstract


Recently, accumulating evidences indicated that microRNA-141 (miR-141) is associated with NPC due to their abilities to affect the expression of genes that modulate tumorigenesis. Unfortunately, there is still limited publication about miR-141 expression in Vietnamese nasopharyngeal cancer patients. In this study, we adopted bioinformatics tools, such as Pictar, Target Scan, miRDB, etc. to predict its target gene. As the results, PTEN (phosphatase and tensin homolog gene), acts oncogenic role associated with biological processes lead to the nasopharyngeal carcinogenesis, was identified as the direct target of miR-141. Experimentally, we reported the evaluation of miR-141 and PTEN expression in NPC biopsy samples and non-cancerous swab samples. The present study demonstrated that miR-141 was upregulated 9.38 times, and PTEN expression was significantly lowered in NPC biopsy samples compared to non-cancerous epithelial swab samples. Our finding demonstrated that the miR-141 was upregulated and PTEN was down regulated in NPC biopsy samples. In the upcoming research, a larger clinical sample size from patients at each stage of the NPC will be performed to understand the expression pattern of the miR-141 and PTEN for further applied in early diagnosis and prognosis as well as therapeutic of NPC.

Keywords


miR-141, Nasopharyngeal Carcinoma, PTEN.

References