Analysis of differential expression profile of circRNA in pancreatic cancer based on high-throughput sequencing technology

Acta Universitatis Medicinalis Anhui 2023 01 v.58 101-108     font:big middle small

Found programs:

Authors:Fu Xiaowei; Ouyang Yonghao; Hong Le; Sun Gen; Xin Wanpeng; Yi Siqing; Xiao Weidong

Keywords:circular RNA;pancreatic cancer;expression profile;proliferation;migration;invasion

DOI:10.19405/j.cnki.issn1000-1492.2023.01.017

〔Abstract〕 Objective To screen the differential expression profile of circular RNA(circRNA) in pancreatic cancer and analyze its potential function. Methods Four pairs of pancreatic cancer tissues and corresponding adjacent pancreatic tissues were selected for high-throughput sequencing, and the differentially expressed circRNA was screened according to fold change>2 and P<0.05. qRT-PCR was used to detect the expression of 5 randomly selected differentially expressed circRNA in 20 pairs of pancreatic cancer tissue samples. GO and KEGG enrichment analysis of differentially expressed circRNA was performed, and the top 50 circRNA-microRNA interaction network was constructed. The relationship between hsa_circ_0046523 and the clinicopathological features of pancreatic cancer was further analyzed, and the effects of hsa_circ_0046523 on the proliferation, migration and invasion of pancreatic cancer cells were observed by functional experiments. Results A total of 17 182 circRNA were predicted by high-throughput sequencing, of which 302 circRNA were differentially expressed including 137 circRNA were upregulated and 165 circRNA were downregulated in pancreatic cancer tissues. The qRT-PCR results showed that the expression levels of hsa_circ_0046523, hsa_circ_0004220 and hsa_circ_0000690 in pancreatic cancer tissues were significantly upregulated(P<0.05), while the expression levels of hsa_circ_0008676 and hsa_circ_0004416 were significantly downregulated(P<0.05), which was consistent with the sequencing results. GO analysis indicated that differentially expressed circRNA were mainly involved in substrate-dependent cell migration, protein kinase complex and cytoskeletal protein binding. KEGG pathway enrichment analysis showed that differentially expressed circRNA were mainly involved in protein digestion and absorption, ABC transporters, central carbon metabolism in cancer, and glycine, serine and threonine metabolism pathways. The expression level of hsa_circ_0046523 was closely correlated with tumor differentiation(P=0.002), T stage(P=0.006), lymph node metastasis(P=0.011) and TNM stage(P=0.001). Compared with HPDE6-C7 cells, the expression of hsa_circ_0046523 significantly increased in pancreatic cancer SW1990, Mia PaCa-2, BxPC-3 and Capan-2 cells(P<0.05). hsa_circ_0046523 knockdown significantly inhibited the proliferation, migration and invasion of pancreatic cancer Mia PaCa-2 BxPC-3 cells(P<0.05). Conclusion There are characteristic differentially expressed circRNAs in pancreatic cancer tissues, and these differentially expressed circRNAs may be involved in the occurrence and development of pancreatic cancer.