LncRNA EPB41L4A-AS2 represses Nasopharyngeal Carcinoma Metastasis by binding to YBX1 in the Nucleus and Sponging MiR-107 in the Cytoplasm

Abstract

Nasopharyngeal carcinoma (NPC) is known for its potential to progress to the lymph nodes and distant metastases at an early stage. As an important regulator in tumorigenesis biological processes, the functions of lncRNA in NPC tumor development remain largely unclear. In this research, the expression of EPB41L4A-AS2 in NPC tissues and cells was analyzed via real-time quantitative polymerase chain reaction (qRT-PCR). CCK8, colony formation, and EDU experiments were used to determine the viability of NPC cells. Transwell and wound healing assays were performed to test NPC cell migration and invasion. RNA pull-down and mass spectrometry analysis were used to identify potential binding proteins. Then, a popliteal lymph node metastasis model was established to test NPC metastasis. EPB41L4A-AS2 is repressed by transforming growth factor-beta, which is downregulated in NPC cells and tissue. It is associated with the presence of distant metastasis and adverse outcomes. The univariate and multivariate survival assays confirmed that EPB41L4A-AS2 expression was an independent predictor of progression-free survival (PFS) in patients with NPC. Biological analyses showed that overexpression of EPB41L4A-AS2 reduced the metastasis and invasion of NPC in vitro and in vivo , but had no significant effect on cell proliferation. Mechanistically, in the nucleus we identified that EPB41L4A-AS2 relies on binding to YBX1 to reduce the stability of Snail mRNA to enhance the expression of E-cadherin and reverse the progression of epithelial-to-mesenchymal transition (EMT). In the cytoplasm, we found that EPB41L4A-AS2 blocked the invasion and migration of NPC cells by promoting LATS2 expression via sponging miR-107. In a whole, the findings of this study help to further understand the metastasis mechanism of NPC and could help in the prevention and treatment of NPC metastasis.

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

“…Additionally, HIF1A-AS1 recruits pYB-1 to the mRNA of HIF1α , promoting its translation, facilitating glycolysis and enhancing the resistance of pancreatic cancer cells to gemcitabine (a nucleoside antimetabolite) [ 128 ]. Likewise, lncRNAs that interact with YB-1 have been successively identified in liver cancer [ 129 ], gastric cancer [ 130 ], lymphoma [ 131 ], nasopharyngeal cancer [ 132 ], esophageal squamous cell carcinoma [ 133 ], melanoma [ 134 ], and clear cell renal cell carcinoma [ 135 ]. In addition, lncRNA PVT1 indirectly promotes YB-1 expression by sponging miR-216a-5p in colorectal cancer [ 136 ].…”

Structural variants in the Epb41l4a locus may cause disruption of TADs, misregulation of the Nrep gene, and neurodevelopmental outcomes

“…It encodes a membrane protein implicated in cytoskeletal regulation, intracellular tra cking, and WNT/β-catenin signaling 11 . Various coding isoforms and long noncoding RNA transcripts of EPB41L4A, such as EPB41L4A-AS1 and EPB41L4A-AS2, play a role in controlling cancer cell proliferation and migration [12][13][14] . According to the IMPC data (https://www.mousephenotype.org/), knockout mice are viable, but they exhibit abnormal kidney morphology, reduced circulating glucose levels, increased heart weight, and decreased grip strength.…”

Unboxing the network among long non-coding RNAs and TGF-β signaling in cancer

“…Knockdown of lnc-PNRC2-1 reduced the expression of EMT markers, although the mechanisms of lnc-PNRC2-1- modulating EMT and TGF-β signaling remain to be clarified. On the other hand, EPB41L4A-AS2 is a lncRNA whose expression is attenuated by TGF-β signaling in nasopharyngeal carcinoma cells ( 45 ). Overexpression of EPB41L4A-AS2 reduced the motility of HNSCC cells in culture and in vivo , and mechanistically, EPB41L4A-AS2 bound to YBX1 in the nucleus, to reduce the stability of SNAI1 mRNA, decreasing EMT progression, while in the cytoplasm, EPB41L4A-AS2 sponged miR-107 , promoting LATS2 expression.…”