본문 바로가기
KERD
논문KCI 등재

Posttranscriptional deregulation of Src due to aberrant miR34a and miR203 contributes to gastric cancer development

1

조회

0

다운로드

1

인용

0

참고문헌

키워드

주제분류화학

초록

Gastric cancer remains the main cause of cancer death all around the world, and upregulated activation of the nonreceptor tyrosine kinase c-SRC (SRC) is a key player in the development. In this study, we found that expression of Src is also increased in clinical gastric cancer samples, with the protein level increased more significantly than that at the RNA level. Further study revealed that miR34a and miR203, two tumor suppressive miRNAs, inversely correlate with the expression of Src. Restoration of miR34a and miR203 decreased Src expression in gastric cancer cell lines, which in turn inhibited cell growth and cell migration. In summary, our study here revealed that posttranscriptional regulation of Src contributes to the deregulated cell growth and metastasis in gastric cancer, and targeting Src by miR34a or miR203 mimics would be a promising strategy in therapy.

Abstract

Gastric cancer remains the main cause of cancer death all around the world, and upregulated activation of the nonreceptor tyrosine kinase c-SRC (SRC) is a key player in the development. In this study, we found that expression of Src is also increased in clinical gastric cancer samples, with the protein level increased more significantly than that at the RNA level. Further study revealed that miR34a and miR203, two tumor suppressive miRNAs, inversely correlate with the expression of Src. Restoration of miR34a and miR203 decreased Src expression in gastric cancer cell lines, which in turn inhibited cell growth and cell migration. In summary, our study here revealed that posttranscriptional regulation of Src contributes to the deregulated cell growth and metastasis in gastric cancer, and targeting Src by miR34a or miR203 mimics would be a promising strategy in therapy.

참고문헌 (24)

  1. Siegel, R., "Cancer statistics, 2012", CA Cancer J. Clin, 62, pp.10~29 (2012)
  2. Le, X. F, "Src family kinases and paclitaxel sensitivity", Cancer Biol. Ther, 12, pp.260~269 (2011)
  3. Aleshin, A., "SRC : a century of science brought to the clinic", Neoplasia, 12, pp.599~607 (2010)
  4. Wheeler, D. L., "The role of Src in solid tumors", Oncologist, 14, pp.667~678 (2009)
  5. Ishizawar, R., "c-Src and cooperating partners in human cancer", Cancer Cell, 6, pp.209~214 (2004)
  6. Yang, G., "RNA-binding protein quaking, a critical regulator of colon epithelial differentiation and a suppressor of colon cancer", Gastroenterology, 138, pp.231~240 (2010)
  7. Wightman, B., "Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans", Cell, 75, pp.855~862 (1993)
  8. Lee, R. C., "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14", Cell, 75, pp.843~854 (1993)
  9. Bartel, D. P., "MicroRNAs : genomics, biogenesis, mechanism, and function", Cell, 116, pp.281~297 (2004)
  10. Calin, G. A., "MicroRNA signatures in human cancers", Nat. Rev. Cancer, 6, pp.857~866 (2006)
  11. Esquela-Kerscher, A., "Oncomirs - microRNAs with a role in cancer", Nat. Rev. Cancer, 6, pp.259~269 (2006)
  12. Kato, M., "The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells", Oncogene, 28, pp.2419~2424 (2009)
  13. Roy, S., "Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF", J. Hematol. Oncol, 5, pp.58~ (2012)
  14. Kasinski, A. L., "miRNA-34 prevents cancer initiation and progression in a therapeutically-resistant K-ras and p53-induced mouse model of lung adenocarcinoma", Cancer Res, 72, pp.5576~5587 (2012)
  15. Wang, C., "MicroRNA- 203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells", J. Exp. Clin. Cancer Res, 31, pp.58~ (2012)
  16. Summy, J. M., "Src family kinases in tumor progression and metastasis", Cancer Metastasis Rev, 22, pp.337~358 (2003)
  17. Okamoto, W., "Identification of c-Src as a potential therapeutic target for gastric cancer and of MET activation as a cause of resistance to c-Src inhibition", Mol. Cancer Ther, 9, pp.1188~1197 (2010)
  18. Grimson, A., "MicroRNA targeting specificity in mammals: determinants beyond seed pairing", Mol. Cell, 27, pp.91~105 (2007)
  19. Garofalo, M., "EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers", Nat. Med, 18, pp.74~82 (2012)
  20. Saini, S., "Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer", Cancer Prev. Res. (Phila), 4, pp.1698~1709 (2011)
  21. Li, N., "Increased miR-222 in H. pylori-associated gastric cancer correlated with tumor progression by promoting cancer cell proliferation and targeting RECK", FEBS Lett, 586, pp.722~728 (2012)
  22. Zauli, G., "miR-34a induces the downregulation of both E2F1 and B-Myb oncogenes in leukemic cells", Clin. Cancer Res, 17, pp.2712~2724 (2011)
  23. Yang, G., "E2F1 and RNA binding protein QKI comprise a negative feedback in the cell cycle regulation", Cell Cycle, 10, pp.2703~2713 (2011)
  24. Oukka, M., "Schnurri-3 (KRC) interacts with c-Jun to regulate the IL-2 gene in T cells", J. Exp. Med, 199, pp.15~24 (2004)

관련 논문AI추천

miR-29a suppresses growth and invasion of gastric cancer cells in vitro by targeting VEGF-AHang Song, Hong Xiao, Hui Ren, Ling Chen, Yi Huang, Zi-Peng Liu, Zong-Hua Wang생화학분자생물학회 · BMB Reports2014 · 제47권 제1호Different MicroRNA Expression Levels in Gastric Cancer Depending on Helicobacter pylori Infection윤혁, 장훈, 김나영, 김정민, 남영희, 박영수, 박지현, 신철민, 이동호, 이혜승, 최윤정거트앤리버 소화기연관학회협의회 · Gut and Liver2015 · 제9권 제2호Long Noncoding RNA N-BLR Upregulates the Migration and Invasion of Gastric Adenocarcinoma윤정호, Chan Hyuk Park, Hyo Joo Byun, Sang Kil Lee, Young Hoon Youn거트앤리버 소화기연관학회협의회 · Gut and Liver2019 · 제13권 제4호Downregulated microRNAs in the colorectal cancer: diagnostic and therapeutic perspectivesAna Rosa Rama, Consolación Melguizo, Ester Sánchez-Jiménez, Jose Prados, Rosa Hernández생화학분자생물학회 · BMB Reports2018 · 제51권 제11호Helicobacter pylori Is Associated with miR-133a Expression through Promoter Methylation in Gastric CarcinogenesisHyo-Joon Yang, Hyun Chae Jung, Ji Min Choi, Joo Hyun Lim, Joo Sung Kim, Sang Gyun Kim거트앤리버 소화기연관학회협의회 · Gut and Liver2018 · 제12권 제1호MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTENAngang Yang, Huayu Zhu, Jing Zhao, Lei Wang, Lintao Jia, Wendong Bai, Xiao Zhang, Xingming Ye, Ying Chen생화학분자생물학회 · BMB Reports2014 · 제47권 제5호

이 간행물의 다른 논문 (6건)