miR‑1303 promotes the proliferation, migration and invasion of prostate cancer cells through regulating the Wnt/β‑catenin pathway by targeting DKK3

Abstract

MicroRNA-1303 (miR-1303) is involved in the tumorigenesis and progression of several cancers, and yet the role of miR-1303 in prostate cancer (PCa) and its underlying mechanism are unknown. To explore this issue, the present study aimed to use PCa tissues, cell lines and a PCa-engrafted mouse model to determine the expression and roles of miR-1303 in PCa. Furthermore, a series of experiments were conducted to explore the underlying mechanisms of action of miR-1303 in PCa cells. miR-1303 was demonstrated to be highly expressed in PCa tissues and cell lines. The level of miR-1303 expression was closely associated with higher Gleason scores and a more developed tumor stage in patients with PCa, and patients with higher levels of miR-1303 displayed a reduced overall survival rate. miR-1303 overexpression promoted the proliferation, migration and invasion of PCa cells. In vivo experiments showed that miR-1303 inhibition suppressed the growth of PCa tumors in mice. Additionally, dickkopf Wnt signaling pathway inhibitor 3 (DKK3) was identified as a target of miR-1303. Knockdown of miR-1303 suppressed the proliferation, migration and invasion of PCa cells, increased DKK3 expression, and inhibited the activity of the Wnt/β-catenin pathway. In conclusion, miR-1303 may promote proliferation, migration and invasion of PCa cells through activating the Wnt/β-catenin pathway by regulating DKK3 expression. These results indicated that miR-1303 may be considered as a potential biomarker for PCa treatment.

Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3

“…DKK3 could induce cellular quiescence in prostate cancer cells through activating the p38MAPK signaling pathway [ 9 ]. Further, it was noted that DKK3 mediated Wnt/β-catenin pathway and thereby suppressed in cellular processes in prostate cancer and hepatocellular carcinoma, incorporating with miRNA [ 10 , 11 ]. However, the role of DKK3 that regulating by LINC00261 in the development of prostate cancer was unknown.…”

Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids

“…In general, the Dickkopf family members are inhibitors of Wnt signaling, such as DKK1 (Glinka et al, 1998;Kruithof-De Julio et al, 2013). However, DKK3 is the most structurally divergent member of the Dickkopf family (Krupnik et al, 1999) and has varied effects on Wnt, ranging from no effect (Krupnik et al, 1999;Pinho Christof Niehrs, 2007;Romero et al, 2013) to promoting (Ferrari et al, 2019;Nakamura and Hackam, 2010;Yin et al, 2018) or inhibiting Wnt activity (Bhattacharyya et al, 2017;Leonard et al, 2017;Liu et al, 2019;Sharma Das et al, 2013). DKK3 also functions as both a positive and negative regulator of TGFb signaling, depending on the model (Al Shareef et al, 2018;Busceti et al, 2017;Kardooni et al, 2018;Li et al, 2017;Pinho Christof Niehrs, 2007;Romero et al, 2013;Wang et al, 2015b), but DKK3 did not impact TGFb in this study (data not shown).…”

The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer

“…By targeting Dickkopf WNT signaling pathway inhibitor 3 (DKK3), miR-1303 is known to activate Wnt/β-catenin signaling and facilitate prostate cancer progression by regulating proliferation, migration, and invasion [ 92 ]. Furthermore, in neuroblastoma cells, it was noted that miR-1303 targets both glycogen synthase kinase-3 beta (GSK3β) and secreted frizzled-related protein 1 (SFRP1), which are endogenous inhibitors of Wnt/β-catenin.…”