<p>Knockdown of lncRNA ABHD11-AS1 Suppresses the Tumorigenesis of Pancreatic Cancer via Sponging miR-1231</p>

Abstract

Background Pancreatic cancer ranks first among the most aggressive malignancies. Long non-coding RNA (LncRNA) ABHD11-AS1 is known to be upregulated in pancreatic cancer. However, the mechanism by which ABHD11-AS1 mediates the tumorigenesis of pancreatic cancer remains unclear. Methods Gene and protein expressions in pancreatic cancer cells were detected by qRT-PCR and Western blot, respectively. Cell viability was measured by CCK-8 assay. Cell apoptosis and cycle were tested by flow cytometry. In addition, cell migration and invasion were tested by wound healing and transwell assay, respectively. The correlation between ABHD11-AS1, miR-1231 and cyclin E1 was confirmed by dual-luciferase report and RNA pull-down. Finally, xenograft mice model was established to investigate the role of ABDH-AS1 in pancreatic cancer in vivo. Results ABHD11-AS1 was found to be negatively correlated with the survival rate of patients with pancreatic cancer. ABHD11-AS1 silencing significantly inhibited the proliferation and induced the apoptosis of pancreatic cancer cells. Additionally, knockdown of ABHD11-AS1 greatly inhibited the migration and invasion of pancreatic cancer cells. Meanwhile, ABHD11-AS1 bound to miR-1231 and cyclin E1 was found to be the target of miR-1231. Moreover, ABHD11-AS1 knockdown-induced G1 arrest in pancreatic cancer cells was reversed by miR-1231 antagomir. Finally, knockdown of ABHD11-AS1 obviously inhibited the tumor growth of pancreatic cancer in vivo. Conclusion ABHD11-AS1 silencing significantly inhibited the tumorigenesis of pancreatic cancer in vitro and in vivo. Thus, ABHD11-AS1 may serve as a potential target for the treatment of pancreatic cancer.

ABHD11-AS1: An Emerging Long Non-Coding RNA (lncRNA) with Clinical Significance in Human Malignancies

“…As of today, lncRNAs have been exploited as the biomarkers for the clinical diagnosis and treatment of various cancers, including PC [ 58 , 59 ]. One such circulatory lncRNA is ABHD11-AS1, which was recently studied for its significance in PC progression, diagnosis, and treatment [ 24 , 25 , 26 ]. In 2018, Qiao X. et al reported that ABHD11-AS1 was significantly upregulated in different PC cell lines (CFPAC-1, BXPC-3, L3.6pl, and PANC-1) and 147 PC patient tissues in comparison to pancreatic cell line (HPDE6-C7) and matched normal pancreatic tissues, respectively [ 24 ].…”

“…Interestingly, the high expression of ABHD11-AS1 correlated clinically with distant metastasis, TNM stage, tumor differentiation, and a five-year reduction in overall survival of PC patients. Similarly, the analysis of TCGA gene expression data for PC also revealed that ABHD11-AS1 was highly expressed and negatively correlated with survival rate in patients with PC [ 26 ].…”

“…Moreover, the knockdown of ABHD11-AS1 in three PC cell lines (L3.6pl, MiaPaCa-1, and PANC-1) resulted in decreased cell proliferation, colony formation, and metastasis (migration and invasion) with increased apoptosis [ 24 , 26 ]. Targeted knockdown of ABHD11-AS1 significantly repressed the in vivo growth of PANC-1 cells injected subcutaneously into a nude mice xenograft model [ 26 ].…”

“…Moreover, the knockdown of ABHD11-AS1 in three PC cell lines (L3.6pl, MiaPaCa-1, and PANC-1) resulted in decreased cell proliferation, colony formation, and metastasis (migration and invasion) with increased apoptosis [ 24 , 26 ]. Targeted knockdown of ABHD11-AS1 significantly repressed the in vivo growth of PANC-1 cells injected subcutaneously into a nude mice xenograft model [ 26 ]. Liu Y. et al identified that the expression levels of circulatory ABHD11-AS1 lncRNA alone or combined with carbohydrate antigen 19-9 (CA199) in the plasma are potential biomarkers for early detection of PC [ 25 ].…”

“…However, the direct target of ABHD11-AS1/miR-133a-3p in OC still needs to be investigated. ABHD11-AS1 sponges miR-361-3p [ 18 ], miR-1231 [ 26 ], and miR-330-5p [ 36 ] to exhibit oncogenic effects via targeting PDPK1 , CCNE1 (cyclin E1), and MARK2 in GC, PC, and CC, respectively. The current literature indicates that ABHD11-AS1 acts as ceRNA by sponging miRNAs to exert oncogenic effects in human cancers, and could be a potential therapeutic target.…”