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.
Highlights
Pancreatic adenocarcinoma (PAAD), one of the most prevailing malignant tumors in digestive system, is defined as one of the main culprits of cancer-associated mortality, which constitutes 1–2% of generalized malignancies, which results in more than 227,000 deaths each year worldwide[1]
LINC01232 knockdown decreased transmembrane 9 superfamily member 2 (TM9SF2) mRNA stability and the rebound of TM9SF2 stability occurred with upregulation of eukaryotic translation initiation factor 4A3 (EIF4A3) (Fig. 5f). These findings revealed that LINC01232 modulated TM9SF2 expression through recruiting EIF4A3 to enhance the mRNA stability of TM9SF2
Pancreatic cancer is characterized by lack of early diagnosis and poor prognosis and its morbidity is increasing annually worldwide[18,19]
Summary
Pancreatic adenocarcinoma (PAAD), one of the most prevailing malignant tumors in digestive system, is defined as one of the main culprits of cancer-associated mortality, which constitutes 1–2% of generalized malignancies, which results in more than 227,000 deaths each year worldwide[1]. Despite surgery is one of the appropriate therapeutic regimens for patients with pancreatic adenocarcinoma, but only 10–20% of patients can be surgically resected in view of lacking main signs or symptoms in the early stages and its aggressive malignant behavior[2]. Long noncoding RNAs (lncRNAs) are a kind of RNA molecules longer than 200 nucleotides without proteincoding potential[5]. Accumulating evidence has exposed that lncRNAs are involved in the initiation and development of numerous malignancies, including pancreatic adenocarcinoma[6,7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
