PT  - JOURNAL ARTICLE
AU  - Hossein Tabatabaeian
AU  - Shen Kiat Lim
AU  - Tinghine Chu
AU  - Sock Hong Seah
AU  - Yoon Pin Lim
TI  - WBP2 inhibits microRNA biogenesis via interaction with the microprocessor complex
AID  - 10.26508/lsa.202101038
DP  - 2021 Jul 01
TA  - Life Science Alliance
PG  - e202101038
VI  - 4
IP  - 7
4099  - https://www.life-science-alliance.org/content/4/7/e202101038.short
4100  - https://www.life-science-alliance.org/content/4/7/e202101038.full
SO  - Life Sci. Alliance2021 Jul 01; 4
AB  - WBP2 is an emerging oncoprotein with diverse functions in breast tumorigenesis via regulating Wnt, epidermal growth factor receptor, estrogen receptor, and Hippo. Recently, evidence shows that WBP2 is tightly regulated by the components of the miRNA biogenesis machinery such as DGCR8 and Dicer via producing both WBP2’s 3′UTR and coding DNA sequence-targeting miRNAs. This led us to hypothesize that WBP2 could provide a feedback loop to the biogenesis of its key upstream regulators by regulating the microprocessor complex activity. Indeed, WBP2 suppressed microprocessor activity by blocking the processing of pri-miRNAs to pre-miRNAs. WBP2 negatively regulated the assembly of the microprocessor complex via physical interactions with its components. Meta-analyses suggest that microprocessor complex components, in particular DGCR8, DDX5, and DEAD-Box Helicase17 (DDX17), have tumor-suppressive properties. 2D and 3D in vitro proliferation assays revealed that WBP2 blocked the tumor-suppressive properties of DGCR8, a key component of the microprocessor complex. In conclusion, WBP2 is a novel regulator of miRNA biogenesis that is a known dysregulated pathway in breast tumorigenesis. The reregulation of miRNA biogenesis machinery via targeting WBP2 protein may have implications in breast cancer therapy.