JOURNAL BROWSE
Search
Advanced SearchSearch Tips
miR-101 Inhibiting Cell Proliferation, Migration and Invasion in Hepatocellular Carcinoma through Downregulating Girdin
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Molecules and Cells
  • Volume 39, Issue 2,  2016, pp.96-102
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2161
 Title & Authors
miR-101 Inhibiting Cell Proliferation, Migration and Invasion in Hepatocellular Carcinoma through Downregulating Girdin
Cao, Ke; Li, Jingjing; Zhao, Yong; Wang, Qi; Zeng, Qinghai; He, Siqi; Yu, Li; Zhou, Jianda; Cao, Peiguo;
  PDF(new window)
 Abstract
miR-101 is considered to play an important role in hepatocellular carcinoma (HCC), but the underlying molecular mechanism remains to be elucidated. Here, we aimed to confirm whether Girdin is a target gene of miR-101 and determine the tumor suppressor of miR-101 through Girdin pathway. In our previous studies, we firstly found Girdin protein was overexpressed in HCC tissues, and it closely correlated to tumor size, T stage, TNM stage and Edmondson-Steiner stage of HCC patients. After specific small interfering RNA of Girdin was transfected into HepG2 and Huh7.5.1 cells, the proliferation and invasion ability of tumor cells were significantly inhibited. In this study, we further explored the detailed molecular mechanism of Girdin in HCC. Interestingly, we found that miR-101 significantly low-expressed in HCC tissues compared with that in matched normal tissues while Girdin had a relative higher expression, and miR-101 was inversely correlated with Girdin expression. In addition, after miR-101 transfection, the proliferation, migration and invasion abilities of HepG2 cells were weakened. Furthermore, we confirmed that Girdin is a direct target gene of miR-101. Finally we confirmed Talen-mediated Girdin knockout markedly suppressed cell proliferation, migration and invasion in HCC while downregulation of miR-101 significantly restored the inhibitory effect. Our findings suggested that miR-101/Girdin axis could be a potential application of HCC treatment.
 Keywords
Girdin;invasion and metastasis;miR-101;primary hepatocellular carcinoma cell;proliferation;
 Language
English
 Cited by
1.
Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity, Biochemical and Biophysical Research Communications, 2017, 483, 1, 509  crossref(new windwow)
2.
Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5, International Journal of Cancer, 2017, 141, 2, 364  crossref(new windwow)
3.
New Insights into the Epigenetics of Hepatocellular Carcinoma, BioMed Research International, 2017, 2017, 1  crossref(new windwow)
4.
miR-101 suppresses HBV replication and expression by targeting FOXO1 in hepatoma carcinoma cell lines, Biochemical and Biophysical Research Communications, 2017, 487, 1, 167  crossref(new windwow)
 References
1.
Anai, M., Shojima, N., Katagiri, H., Ogihara, T., Sakoda, H., Onishi, Y., Ono H., Fujishiro, M., Fukushima, Y., Horike, N., et al. (2005). A novel protein kinase b (pkb)/akt-binding protein enhances pkb kinase activity and regulates DNA synthesis. J. Biol. Chem. 280, 18525-18535. crossref(new window)

2.
Cao, K., Jiang, W., Cao, P., Zou, Q., Xiao, S., Zhou, J., and Huang, C. (2014). Talen-mediated girdin knockout downregulates cell proliferation, migration and invasion in human esophageal carcinoma eca109 cells. Mol. Med. Rep. 10, 848-854. crossref(new window)

3.
Cao, K., Lu, C., Han, S., Zou, Q., Li, J., Xie, D., He, S., Yu, L., Zhou, J., Peng, X., et al. (2015). Expression of Girdin in primary hepatocellular carcinoma and its effect on cell proliferation and invasion. Int. J. Clin. Exp. Pathol. 8, 551-559.

4.
Enomoto, A., Murakami, H., Asai, N., Morone, N., Watanabe, T., Kawai, K., Murakumo, Y., Usukura, J., Kaibuchi, K., and Takahashi, M. (2005). Akt/pkb regulates actin organization and cell motility via girdin/ape. Dev. Cell. 9, 389-402. crossref(new window)

5.
Jin, F., Liu, C., Guo, Y., Chen, H., and Wu, Y. (2013). Clinical implications of Girdin and PI3K protein expression in breast cancer. Oncol Lett. 5,1549-1553. crossref(new window)

6.
Kim, K., Kim, J.H., Kim, I., Lee, J., Seong, S., Park, Y.W., and Kim, N. (2015). MicroRNA-26a regulates RANKL-induced osteoclast formation. Mol. Cells 38, 75-80.

7.
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A.O., Landthaler, M., et al. (2007). A mammalian microrna expression atlas based on small RNA library sequencing. Cell 129, 1401-1414. crossref(new window)

8.
Le-Niculescu, H., Niesman, I., Fischer, T., DeVries, L., and Farquhar, M.G. (2005). Identification and characterization of GIV, a novel Galpha i/s-interacting protein found on COPI, endoplasmic reticulum- Golgi transport vesicles. J. Biol. Chem. 280, 22012- 22020. crossref(new window)

9.
Lin, X., Guan, H., Li, H., Liu, J., Wei, G., Huang, Z., Liao, Z., and Li, Y. (2014). MiR-101 inhibits cell proliferation by targeting rac1 in papillary thyroid carcinoma. Biomed. Rep. 2, 122-126. crossref(new window)

10.
Peng, X., Cao, P., Li, J., He, D., Han, S., Zhou, J., Tan, G., Li, W., Yu, F., Yu, J., et al. (2015). MiR-1204 sensitizes nasopharyngeal carcinoma cells to paclitaxel both in vitro and in vivo. Cancer Biol Ther 16, 261-267. crossref(new window)

11.
Siegel, R., Naishadham, D., and Jemal A. (2012). Cancer statistics, 2013. CA. Cancer. J. Clin. 62,10-29. crossref(new window)

12.
Shen, Q., Bae, H.J., Eun, J.W., Kim, H.S., Park, S.J., Shin, W.C., Lee, E.K., Park, S., Park, W.S., Lee, J.Y., et al. (2014). MiR-101 functions as a tumor suppressor by directly targeting nemo-like kinase in liver cancer. Cancer. Lett. 344, 204-211. crossref(new window)

13.
Shibata, T., Matsuo, Y., Shamoto, T., Hirokawa, T., Tsuboi, K., Takahashi, H., Ishiguro, H., Kimura, M., Takeyama, H., and Inagaki, H. (2013). Girdin, a regulator of cell motility, is a potential prognostic marker for esophageal squamous cell carcinoma. Oncol. Rep. 29, 2127-2132. crossref(new window)

14.
Simpson, F., Martin, S., Evans, TM., Kerr, M., James, D.E., Parton, R.G., Teasdale, R.D., and Wicking, C. (2005). A novel hookrelated protein family and the characterization of hook-related protein 1. Traffic 6. 442-458. crossref(new window)

15.
Su, H., Yang, J.R., Xu, T., Huang, J., Xu, L., Yuan, Y., and Zhuang, S.M. (2009). MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 69, 1135-1142.

16.
Tameda, M., Sugimoto, K., Shiraki, K., Yamamoto, N., Okamoto, R., Usui, M., Ito, M., Takei, Y., Nobori, T., Kojima, T., et al. (2014). Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility. Int. J. Oncol. 45, 541-548. crossref(new window)

17.
Wang, C., Lin, J., Li, L., and Wang, Y. (2014). Expression and clinical significance of girdin in gastric cancer. Mol. Clin. Oncol. 2, 425-428. crossref(new window)

18.
Xu, X., Chen, H., Lin, Y., Hu, Z., Mao, Y., Wu, J., Xu, X., Zhu, Y., Li, S., Zheng, X., et al. (2013). MicroRNA-409-3p inhibits migration and invasion of bladder cancer cells via targeting c-Met. Mol. Cells. 36, 62-68. crossref(new window)

19.
Yin, J., Wang, M., Jin, C., and Qi, Q. (2014). miR-101 sensitizes A549 NSCLC cell line to CDDP by activating caspase 3- dependent apoptosis. Oncol. Lett. 7, 461-465. crossref(new window)

20.
Zhang, J., Han, C., Zhu, H., Song, K., and Wu, T. (2013). MiR-101 inhibits cholangiocarcinoma angiogenesis through targeting vascular endothelial growth factor (VEGF). Am. J. Pathol. 182, 1629-1639. crossref(new window)

21.
Zhang, Y.J., Li, A.J., Han, Y., Yin, L., and Lin, M.B. (2014). Inhibition of Girdin enhances chemosensitivity of colorectal cancer cells to oxaliplatin. World J Gastroenterol. 20, 8229-8236. crossref(new window)

22.
Zheng, C., Li, J., Wang, Q., Liu, W., Zhou, J., Liu, R., Zeng, Q., Peng, X., Huang, C., Cao P., et al. (2015). MicroRNA-195 functions as a tumor suppressor by inhibiting CBX4 in hepatocellular carcinoma. Oncol. Rep. 33, 1115-1122. Z crossref(new window)

23.
hou, L., Yang, Z.X., Song, WJ., Li, QJ., Yang, F., Wang, D.S., Zhang, N., and Dou, K.F. (2013). Microrna-21 regulates the migration and invasion of a stem-like population in hepatocellular carcinoma. Int. J. Oncol. 43, 661-669. crossref(new window)