Circular RNA hsa_circRNA_0007334 is Predicted to Promote MMP7 and COL1A1 Expression by Functioning as a miRNA Sponge in Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic cancer remains one of the leading causes of cancer-related deaths worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor. Many circular RNAs (circRNAs) have proven to play vital roles in the physiological and pathological processes of tumorigenesis; however, their biogenesis in PDAC remains unclear. In this study, the expression profiles of circRNAs from 10 PDAC tissues and their paired adjacent nontumor tissues were analyzed through RNA sequencing analysis. An enrichment analysis was employed to predict the functions of the differentially expressed circRNAs. Sequence alignment information and mRNA microarray projects were used to predict the RNA regulatory network. The knockdown of circRNAs by small interfering RNAs followed by wound healing and western blot assays was used to confirm their functions in a PDAC cell line. A total of 278 circRNAs were identified as differentially expressed in PDAC tissue. Of these, we found that hsa_circRNA_0007334 was significantly upregulated and may serve as a competing endogenous RNA to regulate matrix metallopeptidase 7 (MMP7) and collagen type I alpha 1 chain (COL1A1) by the competitive adsorption of hsa-miR-144-3p and hsa-miR-577 to enhance the expression and functions of MMP7 and COL1A1 in PDAC. In vitro experiments confirmed these results. The present study is the first to propose two regulatory pathways in PDAC: hsa_circRNA_0007334–hsa-miR-144-3p–MMP7 and hsa_circRNA_0007334–hsa-miR-577–COL1A1.

Circular RNA circ‑ACACA regulates proliferation, migration and glycolysis in non‑small‑cell lung�carcinoma via miR‑1183 and PI3K/PKB pathway

“…Growing evidence has clarified the fact that circRNAs could serve as the sponges of miRNAs to function in numerous cancers (30,31) and the present research showed that circ-ACACA was mainly expressed in the cytoplasm in NSCLC cells. In this study, miR-1183 was forecasted to be a target of circ-AcAcA and this interaction was confirmed.…”

Roles of circRNAs in the tumour microenvironment

“…Remodelling of the ECM and angiogenesis in cancer stroma can be considered part of the tumour invasion processes. Circ-0007334 regulates MMP-7 and collagen type I alpha 1 chain (COL1A1) by competitively adsorbing miR-144-3p and miR-577 to enhance the expression and functions of MMP-7 and COL1A1 in pancreatic ductal adenocarcinoma (PDAC) [122]. COL1A1 is responsible for encoding ECM remodelling-related collagens, which are the most abundant proteins in the ECM.…”

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

“…MMP7 and MMP26 are the only two members of the matrilysin subfamily. A large number of studies have compared MMP7 expression in PDAC patients with pancreatitis patients and/or healthy controls and have consistently shown that MMP7 levels are elevated in PDAC patients (Table 1) [34][35][36]54,69,91,[97][98][99][100][101][102][103][104]. More importantly, MMP7 levels correlate with metastasis and/or survival in most, but not all, studies.…”