NNT‐AS1 enhances bladder cancer cell growth by targeting miR‐1301‐3p/PODXL axis and activating Wnt pathway

Abstract

As a tumor involved in the urinary system, bladder cancer (BC) seriously threatens human health. Emerging as crucial biomarkers, long noncoding RNAs (lncRNAs) play an important role in the regulation of many cancers. lncRNA NNT-AS1 has been studied in a series of cancers, whereas its role and potential molecular mechanism was poorly understood in BC. Here, we found that NNT-AS1 was upregulated in BC cells. Functionally, the silencing of NNT-AS1 inhibited cell proliferation, migration, invasion, and endothelial-mesenchymal transition. Furthermore, the apoptosis of BC cells was induced upon NNT-AS1 knockdown. Later, miR-1301-3p, the downstream gene of NNT-AS1, was found at a low level in BC cells. In addition, we found that miR-1301-3p targeted to PODXL. PODXL expression downregulated in NNT-AS1-silenced cells was restored by miR-1301-3p inhibition. Importantly, NNT-AS1 was discovered to activate Wnt pathway, and the treatment of LiCl recovered the repressive role of NNT-AS1 silencing in BC cell growth. Through restoration assays, we observed that PODXL overexpressing countervailed NNT-AS1 depletionmediated suppression on BC cell growth and Wnt pathway. These data suggested that NNT-AS1 enhances BC cell growth and activates Wnt pathway by targeting miR-1301-3p/PODXL axis. K E Y W O R D Sbladder cancer, miR-1301-3p, NNT-AS1, PODXL

The Role of Long Non-Coding RNA NNT-AS1 in Neoplastic Disease

“…Current research shows that NNT-AS1 is highly expressed in most tumors, including non-small-cell lung cancer (NSCLC) [ 16 , 17 , 18 , 19 ], lung squamous cell carcinoma (LUSC) [ 20 ], colorectal cancer (CRC) [ 14 ], hepatocellular carcinoma (HCC) [ 21 ], cholangiocarcinoma (CAA) [ 22 , 23 , 24 ], cervical cancer [ 25 , 26 ], osteosarcoma [ 27 , 28 ], bladder cancer [ 29 , 30 ], and glioma [ 31 ]. These results have been verified in the corresponding tumor tissues or tumor cells.…”

“…Among them, the Wnt/β–catenin pathway mainly regulates the fate of cells during development [ 48 ]. As shown in Figure 2 A, a study found that in bladder cancer, NNT-AS1 can up-regulate podocalyxin-like (PODXL) by sponging miR-1301-3p, which in turn activates the Wnt pathway-related proteins, including CDK1, cyclin D1, MYC, AXIN2, and CTNNB1 (β-catenin) [ 29 ]. In CAA, the up-regulated NNT-AS1 can compete with miR-485 to bind to B-cell CLL/lymphoma 9 protein (BCL9), thereby increasing the expression of BCL9 and promoting the proliferation, migration, and invasion of CCA cells [ 22 ].…”

MiR-1301-3p Inhibits Epithelial to Mesenchymal Transition via Targeting RhoA in Pancreatic Cancer

“…For example, miR-1301-3p inhibited Wnt/β-catenin signaling pathway through targeting BCL9 in hepatocellular carcinoma [12] . Similarly, NNT-AS1 promoted bladder cancer cell proliferation by targeting miR-1301-3p/PODXL axis and activating Wnt pathway [13] . Besides, ABHD11-AS1 and LINC01433 upregulated STAT3 level by sponging miR-1301-3p and promoted tumor progression in papillary thyroid carcinoma and hepatocellular carcinoma, respectively [14,15] .…”

Long non‑coding RNA 00858 knockdown alleviates bladder cancer via regulation of the miR‑3064‑5p/CTGF axis

“…With the advancement of RNA-Seq technologies, lncRNAs are closely associated with bladder cancer (21). Previous studies have revealed that LINC00858, a novel lncRNA, was upregulated in several cancers and functioned as a tumor promoter in colorectal cancer, non-small cell lung cancer and osteosarcoma (8,15,(22)(23)(24). LINC00858 promoted cell proliferation, migration and invasion by acting as a ceRNA of microRNA in the aforementioned cancers.…”