WFDC21P promotes triple-negative breast cancer proliferation and migration through WFDC21P/miR-628/SMAD3 axis

Abstract

Long non-coding RNAs (lncRNAs) modulate cell proliferation, cycle, and apoptosis. However, the role of lncRNA-WFDC21P in the tumorigenesis of triple-negative breast cancer (TNBC) remains unclear. Results of this study demonstrated that WFDC21P levels significantly increased in TNBC, which was associated with the poor survival of patients. WFDC21P overexpression significantly promoted TNBC cell proliferation and metastasis. WFDC21P interacted with miR-628-5p, which further suppressed cell proliferation and metastasis by negatively regulating Smad3-related gene expression. Recovery of miR-628-5p weakened the roles of WFDC21P in promoting the growth and metastasis of TNBC cells. Moreover,N6-methyladenosine (m6A) modification upregulated WFDC21P expression in the TNBC cells. WFDC21P and its m6A levels were increased after methyltransferase like 3 (METTL3) overexpression but reduced after METTL3 silencing. The proliferation and metastasis of TNBC cells were promoted by METTL3 overexpression but suppressed by METTL3 silencing. This study demonstrated the vital roles of WFDC21P and its m6A in regulating the proliferation and metastasis of TNBC cells via the WFDC21P/miR-628/SMAD3 axis.

LncRNA WFDC21P interacts with SEC63 to promote gastric cancer malignant behaviors by regulating calcium homeostasis signaling pathway

“…As shown in previous studies, WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis [ 36 ]. On the opposite side, studies showed that WFDC21P promoted lung [ 37 ], breast [ 38 ], and colorectal tumor [ 39 ] malignant behaviors. In this study, WFDC21P was upregulated in both gastric cancer tissues and cell lines.…”

“…Accumulating evidence suggests that non-coding RNAs (ncRNAs) interacted with miRNAs or proteins to act as molecular sponge [ 40 , 41 ]. In previous studies, WFDC21P was reported to bind with miR-4293 [ 37 ] and miR-628 [ 38 ] to regulate lung and breast cancer progression respectively. On the other aspect, studies showed that WFDC21P was activated by transcription factor Nur77 [ 36 ].…”

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR

“…The lower chamber contains 600 μL of 30% FBS medium. The subsequent processing is according to the previous reports 37 , 38 .…”

Unraveling the cross‐talk between N6‐methyladenosine modification and non‐coding RNAs in breast cancer: Mechanisms and clinical implications

“…WFDC21P interacts with miR-628-5p, and significantly accelerates proliferation and migration of TNBC cells via the Smad3 signaling pathway. 70 The METTL3-mediated m6A modification positively regulates LINC00520, which then acts as a sponge for miR-577, leading to elevated POSTN levels and activation of the downstream ILK/AKT/ mTOR pathway, promoting BC cell proliferation, migration, and EMT. 71 Furthermore, METTL14-mediated m6A modification improves the m6A level of the oncogenic molecule lncRNA AC084125.2 in MDA-MB-231 cells and down-regulates its expression, facilitating BC cell migration and invasion.…”

“…In TNBC cells (SUM159 and BT549), METTL3 upregulates lncRNA‐WFDC21P expression and m6A level through m6A modification. WFDC21P interacts with miR‐628‐5p, and significantly accelerates proliferation and migration of TNBC cells via the Smad3 signaling pathway 70 . The METTL3‐mediated m6A modification positively regulates LINC00520, which then acts as a sponge for miR‐577, leading to elevated POSTN levels and activation of the downstream ILK/AKT/mTOR pathway, promoting BC cell proliferation, migration, and EMT 71 .…”