4.7 Article

UHRF1 is regulated by miR-124-3p and promotes cell proliferation in intrahepatic cholangiocarcinoma

Journal

JOURNAL OF CELLULAR PHYSIOLOGY
Volume 234, Issue 11, Pages 19875-19885

Publisher

WILEY
DOI: 10.1002/jcp.28586

Keywords

cell cycle; ICC; miR-124-3p; prognosis; proliferation; UHRF1

Funding

  1. National Basic Research Program of China [2013CB910501]

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Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is abnormally overexpressed in multiple cancers and closely correlated with tumor-promoting effects, such as high proliferation. However, how UHRF1 functions in intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein, we found that UHRF1 is overexpressed in ICC tissues. Downregulated UHRF1 attenuated the transition of the G1/S cell cycleand then suppressed cellproliferation in vitro and tumor growth in vivo. Moreover, upstream regulators of the UHRF1 expression were predicted, and we found that direct binding of miR-124-3p inhibited the UHRF1 expression. Elevated miR-124-3p suppressed proliferation and led to the arrest of the cell cycle. Furthermore, the expression of UHRF1 was positively correlated with PCNA. Clinically, we showed that elevated UHRF1 was associated with poor prognosis, and servedas an independent prognostic factor in ICC patients. Together, these findings demonstrate that UHRF1, regulated by miR-124-3p, acts as a tumor promoter by promoting cell proliferation in ICC.

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