LINC01232 exerts oncogenic activities in pancreatic adenocarcinoma via regulation of TM9SF2

Abstract

Pancreatic adenocarcinoma (PAAD), one of the most prevailing malignant tumors in digestive system, is identified as one of the main culprits of cancer-associated mortality. Despite long intergenic non-protein coding RNA 1232 (LINC01232) is found to be upregulated in TCGA PAAD tissues and associated with poor prognosis, the potential of LINC01232 in PAAD progression still needs more explorations. In this study, LINC01232 was chosen to be the research object in PAAD cellular processes. Functionally, loss-of function assays were carried out and the experimental results indicated that suppression of LINC01232 hindered the deterioration of PAAD by affecting cell proliferation and migration. Furthermore, relationship between LINC01232 and its nearby gene transmembrane 9 superfamily member 2 (TM9SF2) was investigated. The same expression pattern of TM9SF2 in TCGA PAAD samples was observed. It was found that upregulation of LINC01232 could be a crucial factor for the dysregulation of TM9SF2. Mechanistically, LINC01232 recruited EIF4A3 to boost TM9SF2 mRNA stability. Besides, our findings demonstrated that the transcriptional activation of LINC01232 and TM9SF2 was mediated by SP1. Therefore, we concluded that LINC01232 executed carcinogenic properties in PAAD progression via regulation of TM9SF2. In conclusion, this study was the first to unveil the role and molecular mechanism of LINC01232, suggesting LINC01232 as a promising molecular target for pancreatic cancer treatment.

LncRNA PITPNA‐AS1 boosts the proliferation and migration of lung squamous cell carcinoma cells by recruiting TAF15 to stabilize HMGB3 mRNA

“…RNA‐binding proteins (RBPs) are known to exert their functions via interplaying with RNAs to affect stability, expression, function, and cellular location in tumors 9,10 . For instance, LINC01232 exerts promotive properties in pancreatic adenocarcinoma upon TM9SF2 by recruiting EIF4A3 11 . LIN28B‐AS1 activates LIN28B by binding to IGF2BP1 in lung adenocarcinoma 12 .…”

Long noncoding RNA CASC11 promotes hepatocarcinogenesis and HCC progression through EIF4A3‐mediated E2F1 activation

“…Previous studies revealed LncRNAs can recruit RBPs to regulate the downstream genes by changing the stability of their mRNAs. [32][33][34][35] Through dual screening of target prediction and RNA pull down assay, we identified EIF4A3, a vital exon junction complex component that participates in the development of secondary structure of mRNA in the 5′UTR region and promotes the initiation of translation of proteins. 36,37 We confirmed CASC11 could specially bind to EIF4A3, and the binding site was located in fragment of nucleotides 437-654 of CASC11.…”

Long intergenic non‑coding RNA LINC01232 contributes to esophageal squamous cell carcinoma progression by sequestering microRNA‑654‑3p and consequently promoting hepatoma‑derived growth factor expression

“…LINC01232 expression is upregulated in pancreatic adenocarcinoma, and a high level of expression is associated with a poor clinical outcome ( 26 ). LINC01232 functions as an oncogenic lncRNA in pancreatic adenocarcinoma and regulates cell proliferation, apoptosis, migration, invasion and the epithelial-mesenchymal transition ( 26 ). However, the expression and roles of LINC01232 in ESCC have not yet been elucidated.…”

“…Long intergenic non-coding RNA LINC01232 has been identified as a critical regulator of pancreatic adenocarcinoma oncogenesis ( 26 ). However, the involvement of LINC01232 in ESCC has not yet been thoroughly elucidated.…”