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microRNA‐145 downregulates SIP1 ‐expression but differentially regulates proliferation, migration, invasion and Wnt signaling in SW480 and SW620 cells
Author(s) -
Sathyanarayanan Anusha,
Chandrasekaran Karthik Subramanian,
Karunagaran Devarajan
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26365
Subject(s) - wnt signaling pathway , downregulation and upregulation , microrna , ectopic expression , wnt3a , microbiology and biotechnology , cancer research , gene silencing , epithelial–mesenchymal transition , biology , signal transduction , cell growth , chemistry , cell culture , gene , genetics
microRNA‐145 ( miR‐145 ) has been shown to act as a tumor suppressor in colorectal cancer but its role in the regulation of epithelial‐mesenchymal transition (EMT) is unclear. Ectopic expression of miR‐145 suppressed the proliferation, migration and invasion in SW480 but surprisingly enhanced these traits in its metastatic counterpart, SW620 cells, while, anti miR‐145 reversed the effects of miR‐145 in both of these human colorectal cancer cells. In SW480 and SW620 cells, SMAD‐interacting protein 1 ( SIP1 ), was identified as a target of miR‐145 , and its expression was suppressed both at mRNA and protein levels, and siRNA‐ SIP1 mimicked the effects of miR‐145 . Further, re‐introduction of SIP1 alone or its co‐expression with miR‐145 , rescued SW480 and SW620 cells from the effects of miR‐145 , indicating that the distinct functions of miR‐145 might be mediated, in part, through SIP1 . Since Wnt signaling plays an essential role in EMT in CRC progression, the effects of miR‐145 on the expression of Wnt signaling intermediates and EMT markers were studied. Re‐expression of miR‐145 was found to downregulate the expression of CTNNB1, TCF4, CCND1, VIM, and SNAI, but, upregulated CDH1 expression in SW480 cells. On the other hand, miR‐145 exhibited an oncogenic potential in SW620 cells by actuating Wnt signaling and the expression of EMT‐relevant markers. These results strongly hint that the paradoxical functions of miR‐145 in the regulation of proliferation, migration and invasion might be mediated through downregulation of SIP1 , and differential tuning of Wnt signaling and EMT‐mediators.