Circular RNA hsa_circ_0007367 promotes the progression of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression

Abstract

Circular RNAs (circRNAs) play critical regulatory roles in cancer biological processes. Nevertheless, the contributions and underlying mechanisms of circRNAs to pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. Dysregulated circRNAs between cancerous tissues and matched adjacent normal tissues were identified by circRNA microarray in PDAC. The biological effect of hsa_circ_007367 both in vitro and in vivo was demonstrated by gain- and loss-of-function experiments. Further, dual-luciferase reporter and RNA pull-down assays were performed to confirm the interaction among hsa_circ_007367, miR-6820-3p, and Yes-associated protein 1 (YAP1). The expression of hsa_circ_007367 and YAP1 were detected by in situ hybridization (ISH) and immunohistochemistry (IHC) using tissue microarray (TMA) in 128 PDAC samples. We first identified that a novel circRNA, hsa_circ_0007367, was markedly upregulated in PDAC tissues and cells. Functionally, in vivo and in vitro data indicated that hsa_circ_0007367 promotes the proliferation and metastasis of PDAC. Mechanistically, we confirmed that hsa_circ_0007367 could facilitate the expression of YAP1, a well-known oncogene, by sponging miR-6820-3p, which function as a tumor suppresser in PDAC cells. The results of ISH and IHC demonstrated that hsa_circ_0007367 and YAP1 were upregulated in PDAC tissues. Furthermore, clinical data showed that higher hsa_circ_0007367 expression was correlated with advanced histological grade and lymph node metastasis in PDAC patients. In conclusion, our findings reveal that hsa_circ_0007367 acts as an oncogene via modulating miR-6820-3p/YAP1 axis to promote the progression of PDAC, and suggest that hsa_circ_0007367 may serve as a potential therapeutic target for treatment of PDAC.

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment

“…It was revealed that circRTN4 promoted PDAC tumor growth and liver metastasis by interaction with tumor suppressor miR-497-5p in PDAC cells. 191 Other circRNAs have been studied including circNEIL3, 192 hsa_circ_007367, 193 and circRNA_102049. 194 On the other hand, some circRNAs have been reported to suppress the carcinogenesis of PDAC; in vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1, and they have shown that circNFIB1 was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients.…”

“…It was revealed that circRTN4 promoted PDAC tumor growth and liver metastasis by interaction with tumor suppressor miR-497-5p in PDAC cells 191 . Other circRNAs have been studied including circNEIL3, 192 hsa_circ_007367, 193 and circRNA_102049 194 …”

hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1‐mediated THBS1 transcription

“…17 hsa_ circ_0007367 promotes the proliferation and metastasis of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression. 18 THBS1, as a member of the extracellular matrix (ECM) protein family, is an evolutionally conserved calcium-binding glycoprotein with various protein-binding domains. 19 It has multiple biological functions, and not only can regulate angiogenesis but also participate in the biological functions of tumor cell adhesion, invasion, migration, proliferation, apoptosis, and immunity.…”

“…For example, circSTX6 promotes the proliferation and metastasis of pancreatic ductal adenocarcinoma by sponging miR‐449b‐5p and interacting with CUL2 17 . hsa_circ_0007367 promotes the proliferation and metastasis of pancreatic ductal adenocarcinoma by sponging miR‐6820‐3p and upregulating YAP1 expression 18 . THBS1, as a member of the extracellular matrix (ECM) protein family, is an evolutionally conserved calcium‐binding glycoprotein with various protein‐binding domains 19 .…”

Circ_0003945: an emerging biomarker and therapeutic target for human diseases

“…Circ_0003945 (circBase ID: hsa_circ_0003945) was located on chr9: 33953282–33956144, with a total length of 258 nt. It was formed by back-spliced of the 11 and 12 exons of the ubiquitin-associated protein 2 (UBAP2) and aliased hsa_circ_0001846 ( 34 ), hsa_circ_0001850 ( 35 ), hsa_circ_0003141 ( 36 ), hsa_circ_0003496 ( 37 ), hsa_circ_0007367 ( 38 ), hsa_circ_0008344 ( 39 ), and hsa_circ_0086735 ( 40 ) ( Table 1 ). For the sake of narrative clarity in this text, it will be uniformly referred to as circ_0003945.…”