LncRNA TP73‐AS1 regulates miR‐495 expression to promote migration and invasion of nasopharyngeal carcinoma cells through junctional adhesion molecule A

Abstract

The main obstacle to the treatment of nasopharyngeal carcinoma (NPC) is metastasis. Long non‐coding RNAs (lncRNAs) and microRNAs (miRNAs) are highly involved in the progression of NPC. In this study, we aimed to explore the regulatory role of lncRNA P73 antisense RNA 1 T (TP73‐AS1) and miR‐495 in migration and invasion of NPC cells. The expression levels of TP73‐AS1, miR‐495, and junctional adhesion molecule A (JAM‐A) in NPC tissue samples and cell lines were examined by quantitative real‐time PCR (qRT‐PCR) and/or Western blot. NPC cells were transfected with vectors overexpressing TP73‐AS1, short hairpin RNA (shRNA) against TP73‐AS1, shRNA against JAM‐A, miR‐495 mimics, miR‐495 inhibitor, and their corresponding negative controls as designated. The MTT assay, cell migration assay, and transwell assay were performed to detect cell viability, migration, and invasion, respectively. Dual‐luciferase reporter assay was performed to confirm the binding of TP73‐AS1 and miR‐495, and miR‐495 and JAM‐A. TP73‐AS1 and JAM‐A were significantly upregulated while miR‐495 was markedly downregulated in NPC tissues and cell lines compared to normal controls. The overexpression of TP73‐AS1 promoted migration and invasion of NPC cell line CNE‐2. TP73‐AS1 targeted miR‐495 and negatively regulated its expression. TP73‐AS1 upregulated the expression of JAM‐A through miR‐495. TP73‐AS1 mediated migration and invasion of CNE‐2 cells via upregulating JAM‐A. LncRNA TP73‐AS1, miR‐495, and JAM‐A are involved in migration and invasion of NPC cells. The TP73‐AS1/miR‐495/JAM‐A axis may serve as a therapeutic target for the treatment of NPC.

The Roles of Junctional Adhesion Molecules (JAMs) in Cell Migration

“…In the Rip1Tag2 tumor model, Jam-A −/− DCs had a higher rate of DC migration through the endothelium into the tumor than Jam-A +/+ DCs ( Murakami et al, 2010 ). High JAM-A expression induces EMT of nasopharyngeal carcinoma (NPC) cells in vitro and in vivo via the PI3K/Akt pathway, and lncRNA P73 antisense RNA 1 T (TP73-AS1) could upregulate JAM-A expression ( Tian et al, 2015 ; Dai et al, 2021 ). Histone deacetylases (HDACs) inhibitors downregulated p63-mediated JAM-A expression, suppressing the proliferation, migration, and invasiveness of human head and neck squamous cell carcinoma (HNSCC) ( Kakiuchi et al, 2021 ).…”

The Role of lncRNAs in Rare Tumors with a Focus on HOX Transcript Antisense RNA (HOTAIR)

“…More recently, many other lncRNAs have been associated with NPC progression, with their capacity of sponging different microRNAs [ 58 , 61 , 62 , 63 , 71 , 72 , 73 , 74 ]. Additionally, in NPC patients, a large number of lncRNAs were also associated with cisplatin resistance [ 42 , 43 , 44 , 45 , 75 , 76 , 77 , 78 ] and radioresistance [ 54 , 79 , 80 ].…”

Junctional adhesion molecule-A (JAM-A) in gynecological cancers: Current state of knowledge

“…Moreover, it regulates many cellular processes, including angiogenesis (Naik et al, 2008), cell migration (Azari et al, 2010;Wang and Liu, 2022) and adhesion (Mandell et al, 2005), leukocyte transendothelial migration (Corada et al, 2005;Khandoga et al, 2005), intercellular permeability (Laukoetter et al, 2007), epithelial-tomesenchymal transition (EMT) (Communal et al, 2020) and platelet activation (Babinska et al, 2002). In the literature, JAM-A is described as a protein involved in the pathogenesis of neurological disorders (Padden et al, 2007), cardiovascular diseases (Babinska et al, 2019;Koenen and Weber, 2022;Rath et al, 2022;Wang and Chen, 2022), rheumatoid arthritis (Fang et al, 2016), inflammatory bowel disease (Vetrano and Danese, 2009), and many types of neoplastic diseases including breast (McSherry et al, 2009;Murakami et al, 2011;Vellanki et al, 2019;Bednarek et al, 2020;Vences-Catalan et al, 2021;Smith et al, 2022), lung (Magara et al, 2017;Zhao et al, 2017), nasopharyngeal (Jiang et al, 2019;Dai et al, 2021), head and neck (Kurose et al, 2016;Kakiuchi et al, 2021), testicular (Tarulli et al, 2013), thyroid (Orlandella et al, 2019), colorectal (Caykara et al, 2019;Lampis et al, 2021), gastric (Huang et al, 2014), endometrial (Koshiba et al, 2009), cervical (Akimo...…”