Dissection of FOXO1-Induced LYPLAL1-DT Impeding Triple-Negative Breast Cancer Progression via Mediating hnRNPK/β-Catenin Complex

Abstract

Triple-negative breast cancer (TNBC) is considered as the most hazardous subtype of breast cancer owing to its accelerated progression, enormous metastatic potential, and refractoriness to standard treatments. Long noncoding RNAs (lncRNAs) are extremely intricate in tumorigenesis and cancerous metastasis. Nonetheless, their roles in the initiation and augmentation of TNBC remain elusive. Here, in silico analysis and validation experiments were utilized to analyze the expression pattern of clinically effective lncRNAs in TNBC, among which a protective lncRNA LYPLAL1-DT was essentially curbed in TNBC samples and indicated a favorable prognosis. Gain- and loss-of-function assays elucidated that LYPLAL1-DT considerably attenuated the proliferative and metastatic properties along with epithelial-mesenchymal transition of TNBC cells. Moreover, forkhead box O1 (FOXO1) was validated to modulate the transcription of LYPLAL1-DT. Mechanistically, LYPLAL1-DT impinged on the malignancy of TNBC mainly by restraining the aberrant reactivation of the Wnt/β-catenin signaling pathway, explicitly destabilizing and diminishing β-catenin protein by interacting with heterogeneous nuclear ribonucleoprotein K (hnRNPK) and constricting the formation of the hnRNPK/β-catenin complex. Conclusively, our present research revealed the anti-oncogenic effects of LYPLAL1-DT in TNBC, unraveling the molecular mechanisms of the FOXO1/LYPLAL1-DT/hnRNPK/β-catenin signaling axis, which shed innovative light on the potential curative medicine of TNBC.

Crosstalk between lncRNAs and Wnt/β-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response

“…According to a clinical standpoint, a number of studies have pointed out that potential therapeutic and prognostic biomarkers might be molecules connected to the lncRNA-Wnt/β-catenin regulatory axis such as the FOXO1/lncRNA LYPLAL1-DT/hnRNPK/β-catenin signaling axis in triple-negative breast cancer (TNBC) [ 114 ]. It should be acknowledged that there are still a lot of restrictions.…”

Unveiling the therapeutic potential: KBU2046 halts triple-negative breast cancer cell migration by constricting TGF-β1 activation <i>in vitro</i>

“…Breast cancer continues to be the most prevalent cancer among women globally [22]. TNBC is considered the most dangerous breast cancer subtype due to its accelerated progression, vast metastatic potential, and resistance to standard treatments [23,24]. While advanced multi-modal therapy has substantially improved the curability of earlystage breast cancer to 70%-80%, addressing advanced metastatic breast cancer remains a significant challenge [25,26].…”

Research progress of the netrins and their receptors in cancer

“…As one of the most frequent malignant tumours in women globally, breast cancer (BC) poses a major threat to human survival and well‐being. 39 …”