<p>Blocking circ_0013912 Suppressed Cell Growth, Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells in vitro and in vivo Partially Through Sponging miR-7-5p</p>

Abstract

Background: Circular RNAs have been emerging as biomarkers in diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC). The hsa_circ_0013912 (circ_0013912) has been retrieved to be upregulated in PDAC. Here, we further investigated its role in PDAC cells, as well as its mechanism via serving as competing endogenous RNA (ceRNA) for miRNA (miR)-7-5p, which is abundant in pancreas and suppresses the development of PDAC. Materials and Methods: The clinical human tissues were harvested from Gene Expression Omnibus (GEO) database and PDAC patients, and expression of circ_0013912 and miR-7-5p was detected by real-time quantitative PCR. The interaction between both was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and biotin-miRNA pull-down assay. Functional experiments were performed using Cell Counting Kit-8 assay, colony formation assay, fluorescence-activated cell separation method, caspase 3 activity assay kit, Western blotting, transwell assays, and xenograft tumor model. Results: circ_0013912 was upregulated in PDAC tumors and cells; besides, circ_0013912 upregulation was associated with TNM stage and lymph node metastasis. Silencing circ_0013912 inhibited cell viability, colony formation ability, cell cycle entrance, migration and invasion, but facilitated apoptosis rate and caspase 3 activity in PANC-1 and AsPC-1 cells, accompanied with decreased c-myc, cyclin D1 and vimentin, and increased E-cadherin. Furthermore, miR-7-5p was a target of circ_0013912. Blocking miR-7-5p could promote cell growth, migration and invasion of PANC-1 and AsPC-1 cells with circ_0013912 silencing or not. Tumor growth was also restrained by circ_0013912 downregulation. Conclusion: Circ_0013912 knockdown could suppress cell growth and metastasis of PDAC cells via sponging miR-7-5p.

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

“…Pancreatic ductal adenocarcinoma (PDAC) is a typically malignant tumor of the digestive system, with a 5-year overall survival rate of less than 6% [ 36 ]. It is reported that approximately 80% of patients have lost the chance for surgical resection because of its complexity and invisibility [ 36 , 37 ]. Hence, it is imperative to promote the development of early biomarkers and novel therapeutic methods according to the molecular mechanisms for the prognosis of PDAC.…”

The Role of Circular RNAs in Pancreatic Ductal Adenocarcinoma and Biliary-Tract Cancers

“…In those circRNAs found to be overexpressed in PDAC, ectopic or stimulated overexpression generally enhances features of malignancy such as proliferation, viability, migration and invasion whilst inhibiting apoptosis; while silencing and reducing expression attenuates those features of malignancy. In one study, this was supported through measuring markers of proliferation (i.e., c-Myc and cyclin D1), along with markers of invasion and metastasis (i.e., vimentin and E-cadherin) [94]. Conversely, where under expression has been associated with malignancy, ectopic expression has been shown to inhibit colony-forming ability and proliferation, whilst promoting apoptosis.…”

Current State of “Omics” Biomarkers in Pancreatic Cancer

“…Successfully accomplishing multi-omics data integration by systems biology approaches will fulfill future expectations and the need for robust, accurate, and feasible biomarker panels for pancreatic cancer. [166] Tumor tissue hsa_circ_0006215 Upregulated circRNA overexpression [167] Tumor tissue, plasma exosome circ-IARS Upregulated circRNA overexpression [168] Tumor tissue circ-PDE8A Upregulated circRNA overexpression [169] Tumor tissue/cell hsa_circ_0001649 Downregulated Microarray/qRT-PCR [170] Tumor tissue/cell hsa_circ_0005397 (circ-RHOT1) Upregulated Microarray/qRT-PCR [171] Tumor tissue/cell lines hsa_circ_0030235 Upregulated circRNA overexpression [172] Tumor tissue/cell lines hsa_circ_0007534 Upregulated circRNA overexpression [173] Tumor tissue/cell lines ciRS-7 (Cdr1as) Upregulated qRT-PCR [174] Tumor tissue hsa_circ_0007334 Upregulated Microarray/qRT-PCR [175] Tumor tissue circLDLRAD3 Upregulated circRNA knockdown [176] Tumor tissue/cell circASH2L Upregulated Microarray/qRT-PCR [177] Tumor tissue/cell lines circADAM9 Upregulated circRNA knockdown [178] Tumor tissue/cell hsa_circ_001653 Upregulated circRNA knockdown [179] Tumor tissue/cell circHIPK3 Upregulated circRNA knockdown [180] Tumor tissue/cell circFOXK2 Upregulated circRNA knockdown [181] Tumor tissue hsa_circ_0009065 (circBFAR) Upregulated circRNA overexpression [70] Tumor tissue hsa_circ_0086375 (circNFIB1) Downregulated circRNA knockdown [182] Tumor tissue/cell hsa_circ_0013912 Upregulated circRNA overexpression [183] Tumor tissue/cell lines hsa_circ_001587 Downregulated circRNA knockdown [184] Tumor [194] Tumor tissue BC008363 Upregulated Microarray/qRT-PCR [195] Tumor tissue HSATII Upregulated RNA-seq [196] Serum/plasma U2snRNA Upregulated Microarray/qRT-PCR [197] Pancreatic * CZE: capillary zone electrophoresis, ELISA: enzyme-linked immunosorbent assay, ELLA: Enzyme-linked lectin assay, FISH: fluorescence in situ hybridization, GC: gas chromatography, HILIC: Hydrophilic interaction chromatography, HRMAS: high-resolution magic angle spinning, LC: liquid chromatography, MS: mass spectrometry, NMR: nuclear magnetic resonance, qRT-PCR: quantitative reverse transcription polymerase chain reaction, TOF: time of flight, WB: Western blot, WES: Whole exome sequencing, WGS: whole genome ...…”