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  • Zhao, SenlinShanghai Jiao Tong University, Peoples R China (author)

miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGF beta-mediated epithelial to mesenchymal transition

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-01-17
  • BIOMED CENTRAL LTD,2017
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-135399
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-135399URI
  • https://doi.org/10.1186/s12943-017-0585-zDOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|National High Technology Research and Development Program of China [SS2014AA020803]; National Natural Science Foundation of China [81220108021, 81302083, 81272750]; Natural Science Foundation of Shanghai [16ZR1427700]; Project of Shanghai Science and Technology Commission [124119a1700, 14411950502]; Project of Songjiang District [0702 N14001]
  • Background: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. Methods: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGF beta pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. Results: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGF beta signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/ Smad7/TGF beta in vitro and in vivo. Conclusion: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGF beta signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.

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  • Sun, HongchengShanghai Jiao Tong University, Peoples R China (author)
  • Jiang, WeiliangShanghai Jiao Tong University, Peoples R China (author)
  • Mi, YushuaiShanghai Jiao Tong University, Peoples R China (author)
  • Zhang, DongyuanShanghai Jiao Tong University, Peoples R China (author)
  • Wen, YugangShanghai Jiao Tong University, Peoples R China (author)
  • Cheng, DantongShanghai Jiao Tong University, Peoples R China (author)
  • Tang, HuameiShanghai Jiao Tong University, Peoples R China (author)
  • Wu, ShaohanJiaxing Coll, Peoples R China (author)
  • Yu, YangShanghai Jiao Tong University, Peoples R China (author)
  • Liu, XishengShanghai Jiao Tong University, Peoples R China (author)
  • Cui, WeiyingqiLinköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)n/a (author)
  • Zhang, MengFudan University, Peoples R China (author)
  • Sun, Xiao-Feng,1959-Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)xiasu45 (author)
  • Zhou, ZongguangSichuan University, Peoples R China (author)
  • Peng, ZhihaiShanghai Jiao Tong University, Peoples R China (author)
  • Yan, DongwangShanghai Jiao Tong University, Peoples R China (author)
  • Shanghai Jiao Tong University, Peoples R ChinaJiaxing Coll, Peoples R China (creator_code:org_t)

Related titles

  • In:Molecular Cancer: BIOMED CENTRAL LTD161476-4598

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