CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

Abstract Background Circular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. It played different roles in a variety of diseases including cancer and performed different functions. Nonetheless, reports on the specific function of circRNA in pancreatic cancer (PC) were still rarely so far. In particular, the role of circSEC24A in PC remains unclear. Methods Real-time fluorescent quantitative PCR was used to evaluate the expression level of circSEC24A in pancreatic cancer tissues and cell lines. Furthermore, we used some functional experiments, such as EDU and Transwell assays, to explore the effects of circSEC24A on the proliferation and invasiveness of pancreatic cancer. Finally, the corresponding relationship among circSEC24A, miR-606 and TGFBR2 was explored by dual luciferase reporter and other mechanism studies. Results The expression of circSEC24A in both pancreatic cancer tissues and cell lines was evidently up-regulated. Furthermore, knockdown of circSEC24A significantly inhibited the proliferative, migration and invasive capacity of pancreatic cancer cells, whereas miR-606 inhibitor obviously counteracted these effects. Further study confirmed that circSEC24A alleviated suppression on target TGFBR2 expression by directly sponging miR-606 and then influenced the tumorigenesis of pancreatic cancer. Conclusions These findings indicated that the progression of pancreatic cancer can be driven by circSEC24A influencing miR-606/TGFBR2 axis. Therefore, circSEC24A might be used as a critical biomarker influencing the early diagnosis and prognosis of pancreatic cancer.

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SIRT1 promotes the proliferation and metastasis of human pancreatic cancer cells

Tumor Biology ◽

10.1177/1010428317691180 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769118 ◽

Cited By ~ 11

Author(s):

Jianguang Jin ◽

Zhijie Chu ◽

Pengfei Ma ◽

Yuanpu Meng ◽

Yanhui Yang

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Cancer Cell Proliferation ◽

Pancreatic Cancer Cells ◽

Cell Proliferation And Migration ◽

Proliferation And Metastasis ◽

And Migration ◽

Cancer Tissues ◽

Proliferation And Migration

SIRT1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SIRT1 promotes pancreatic cancer tumorigenesis. The aim of this study is to investigate the SIRT1 expression levels and biological functions in promoting pancreatic cancer progression. We first investigated the expression of SIRT1 in a series of pancreatic cancer tissues as well as in a panel of pancreatic cancer cell lines. The effect of SIRT1 on cell activity was explored by knockdown experiments. Cell growth was measured using the MTT assay and colony-formation assay. Migration and invasion were tested using transwell assay. Our results showed that the expression of SIRT1 was significantly up-regulated both in pancreatic cancer tissues and cell lines. Knockdown of SIRT1 suppressed cell proliferation and migration of pancreatic cancer cells. This is the first report to disclose the role of SIRT1 in regulation of pancreatic cancer cell proliferation and migration, which may provide a potential therapeutic target for pancreatic cancer patients.

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CircRNA_000864 Upregulates B-cell Translocation Gene 2 Expression and Represses Migration and Invasion in Pancreatic Cancer Cells by Binding to miR-361-3p

Frontiers in Oncology ◽

10.3389/fonc.2020.547942 ◽

2020 ◽

Vol 10 ◽

Author(s):

Linsheng Huang ◽

Junxiang Han ◽

Huifan Yu ◽

Jialing Liu ◽

Lili Gui ◽

...

Keyword(s):

Cell Cycle ◽

Pancreatic Cancer ◽

Cell Proliferation ◽

Tumor Growth ◽

Expression Patterns ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Pancreatic Cancer Cells ◽

Gene Assay ◽

Cancer Tissues

BackgroundPancreatic cancer is a fatal disease with a very poor prognosis due to its characteristic insidious symptoms, early metastasis, and chemoresistance. Circular RNAs (circRNAs) are involved in the development of pancreatic cancer.AimHence, the aim of this study is to elucidate the mechanism of circRNA_000864 in regulating BTG2 expression in pancreatic cancer by binding to miR-361-3p.MethodsCircRNA_000864, miR-361-3p, and BTG2 expression patterns in the pancreatic cancer tissues were detected by RT-qPCR. Correlation among circRNA_000864, miR-361-3p, and BTG2 was evaluated by RNA-pull down assay, RNA Immunoprecipitation assay, and dual-luciferase reporter gene assay. After ectopic expression and depletion experiments, 5-ethynyl-2′-deoxyuridine assay, Transwell assay, and flow cytometry were employed to assess the cell proliferation, migration and invasion, cell cycle, and apoptosis. Xenotransplantation of nude mice was conducted to detect the effects of circRNA_000864, miR-361-3p, and BTG2 on tumor growth.ResultsCircRNA_000864 and BTG2 were poorly expressed, and miR-361-3p was highly expressed in the pancreatic cancer tissues. CircRNA_000864 bound to miR-361-3p could target BTG2. Cell proliferation, migration, and invasion were inhibited, and the cell cycle arrest and apoptosis were stimulated after overexpression of circRNA_000864 or BTG2 or downregulation of miR-361-3p. Overexpression of circRNA_000864 or downregulation of miR-361-3p also decreased the tumor growth in vivo.ConclusionsConjointly, our findings elicited that the overexpression of circRNA_000864 could promote BTG2 expression to inhibit pancreatic cancer development by binding to miR-361-3p, which represents an appealing therapeutic target for the treatment of pancreatic cancer.

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MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer

Digestion ◽

10.1159/000503225 ◽

2019 ◽

Vol 101 (6) ◽

pp. 794-806 ◽

Cited By ~ 1

Author(s):

Jun Okazaki ◽

Toshihito Tanahashi ◽

Yasushi Sato ◽

Jinsei Miyoshi ◽

Tadahiko Nakagawa ◽

...

Keyword(s):

Pancreatic Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cell Invasion ◽

Poor Prognosis ◽

Cancer Cell Lines ◽

Pancreatic Cancer Cells ◽

Cancer Tissues

Background/Aims: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, and resistance to chemotherapy, leading to a poor prognosis. To clarify the molecular mechanism of these malignant characteristics, we performed a genome-wide microRNA (miRNA) array analysis utilizing micro-cancer tissues from patients with unresectable PDAC (stage IV), obtained by endoscopic ultrasound-fine needle aspiration (EUS-FNA). Methods: The expression profiles of 2,042 miRNAs were determined using micro-cancer tissues from 13 patients with unresectable PDAC obtained by EUS-FNA. The relationship between individual miRNA levels and overall survival (OS) was analyzed. Possible target genes for miRNAs were bioinformatically analyzed using the online database miRDB. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and PK-8 were transfected with miRNA mimic or small interfering RNA, and cell invasion, epithelial-mesenchymal transition (EMT), and apoptosis markers were examined. miRNA and mRNA expressions were examined by quantitative polymerase chain reaction. Results: Of 2,042 miRNAs, the 10 that exhibited the lowest correlation coefficient (p ≤ 0.005) between miRNA expression level and OS among the patients were identified. The miRDB and expression analysis in cancer cell lines for the 10 miRNAs identified miR-296-5p and miR-1207-5p as biomarkers predictive of shorter survival (p < 0.0005). Bioinformative target gene analysis and transfection experiments with miRNA mimics showed that Bcl2-related ovarian killer (BOK), a pro-apoptotic gene, is a target for miR296-5p in pancreatic cancer cells; transfection of miR-296-5p mimic into PANC-1, MIA PaCa-2, and PK-8 cells resulted in significant suppression of BOK mRNA and protein expression. These transfectants showed significantly higher invasion capability compared with control cells, and knock down of BOK in pancreatic cancer cells similarly enhanced invasion capability. Transfectants of miR-296-5p mimic also exhibited aberrant expression of EMT markers, including vimentin and N-cadherin. Moreover, these transfectants showed a significantly lower apoptosis rate in response to 5-fluorouracil and gemcitabine with a decrease of BOK expression, suggesting a role of miR-296-5p in drug resistance. Conclusion: These results suggest that miR-296-5p is a useful biomarker for a poor prognosis in patients with PDAC, and that the miR-296-5p/BOK signaling axis plays an important role in cell invasion, drug resistance, and EMT in PDACs.

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METTL3 Promotes Pancreatic Tumor Progression Through Regulating the miR-196a/CPEB3 Axis

10.21203/rs.3.rs-101231/v1 ◽

2020 ◽

Author(s):

Pingping Ge ◽

Dong Fan ◽

Lei He ◽

Qiong Wu ◽

Jin Sun ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Progression ◽

Cancer Cells ◽

Pancreatic Tumor ◽

Luciferase Reporter ◽

Pancreatic Cancer Cells ◽

And Migration ◽

Proliferation And Migration

Abstract Background: Methyltransferase-like 3(METTL3)-mediated N6-methyladenosine (m6A) modification has been reported to regulate microRNAs maturation. Here, the study was designed to investigate the regulatory effect of m6A-dependent miRNA maturation on pancreatic cancer progression which is still limited before.Results: We found that METTL3 significantly upregulated in the pancreatic tumor tissues. Overexpression of METTL3 promoted cancer cell proliferation and migration in vitro and tumor progression in vivo. METTL3-mediated m6A modification facilitated miR-196a maturation in pancreatic cancer cells, and miR-196a increased the proliferation and migration of cancer cells in vitro. Luciferase reporter assay verified that cytoplasmic polyadenylation element binding protein 3 (CPEB3) was a direct target gene of miR-196a. In vivo studies proved that overexpression of miR-196a inhibited the anti-tumor effect of knockdown of METTL3, and overexpression of CPEB3 inhibited the miR-196a-enhanced tumor progression. Conclusions: We identified that METTL3 was upregulated in pancreatic cancer, leading to the upregulation of miR-196a, resulting in the downregulation of CPEB3, which promoted the pancreatic tumor progression. We first demonstrated that CPEB3 was a tumor suppressor gene in pancreatic cancer, and the METTL3 regulated miR-196a/CPEB3 axis may be a therapeutic target for pancreatic cancer therapy.

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Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells

10.21203/rs.3.rs-46710/v1 ◽

2020 ◽

Author(s):

Yan Xu ◽

Nanbin Liu ◽

Yuhua Wei ◽

Deren Zhou ◽

Rui Lin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Epithelial Mesenchymal Transition ◽

Pancreatic Tumors ◽

Luciferase Reporter ◽

Protective Effects ◽

Mesenchymal Transition ◽

Pancreatic Cancer Cells

Abstract Objective This study aims to explore the roles of miR-124 in pancreatic tumor and potential vehicles. Methods The expression of miR-124 and EZH2 was determined in both pancreatic cancer tissues and cell lines. miR-124 or EZH2 was overexpressed in AsPC-1 and PANC1 cells. Then, the effects on cell viability. apoptosis, invasion, migration and epithelial mesenchymal transition were evaluated. Afterwards, the roles of miR-124 on the expression and function of EZH2 in pancreatic tumors were determined by dual luciferase reporter assay. Subsequently, miR-124 was transfected to bone marrow mesenchymal stromal cells (BM-MSCs), and the BM-MSCs derived exosomes were isolated and co-cultured with AsPC-1 and PANC1 cells, or injected into pancreatic cancer tumor-bearing mice. Results The miR-124 expression levels decreased in pancreatic adenocarcinoma tissues and cancer cell lines AsPC-1, PANC1, BxPC-3 and SW1990. Furthermore, the elevated expression of miR-124 in AsPC-1 and PANC1 via miR-124 mimic transfection-induced apoptosis, metastasis and epithelial mesenchymal transition was suppressed, and the EZH2 overexpression partly reversed the protective effects of miR-124 against pancreatic tumors. In addition, the expression of miR-124 was detected in exosomes extracted from miR-124-transfected BM-MSCs, and these exosomes delivered miR-124 into pancreatic cancer cells, and presented the anti-tumor effects in vitro and in vivo. Conclusion MiR-124-carried BM-MSC-derived exosomes have potential applications for the treatment of pancreatic tumors.

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CCNI2 knockdown inhibits the proliferation, apoptosis and migration of pancreatic cancer cells

10.21203/rs.3.rs-24690/v1 ◽

2020 ◽

Author(s):

Bingyang Hu ◽

Wenzhi Zhang ◽

Changsheng Zhang ◽

Chonghui Li ◽

Ning Zhang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Malignant Tumors ◽

Immunohistochemical Analysis ◽

Proliferation Capacity ◽

Pancreatic Cancer Cells ◽

And Migration ◽

Apoptosis Process ◽

Cancer Tissues ◽

Cyclin I

Abstract Background: Pancreatic cancer has been recognized as one of the most serious malignant tumors in the world, and its molecular mechanism is still not fully understood. Cyclin I-like (CCNI2) is a homolog of Cyclin I (CCNI), and at present its function is largely unknown.Methods: In this study, we aimed to explore the role of CCNI2 in the development of pancreatic cancer. The expression levels of CCNI2 in pancreatic cancer tissues and cells were detected by immunohistochemical analysis and qPCR, respectively. Lentivirus was used to deliver shRNA to pancreatic cancer cells to construct CCNI2 knockdown cell models. MTT and colony formation assays were used to assess cell proliferation capacity, flow cytometry was used to detect apoptosis, wound-healing and Transwell assays were used to determine cell migration.Results: Our results revealed that CCNI2 is not only highly expressed in pancreatic cancer, but also significantly correlated with pathological grade, pathological stage, and survival rate. It was confirmed that knockdown of CCNI2 inhibited the proliferation and cell migration of pancreatic cancer cells while promoting apoptosis. Furthermore, human apoptotic antibody arrays showed that CCNI2 is involved in apoptosis process by up-regulating the pro-apoptotic proteins.Conclusions: In conclusion, CCNI2 may be a prognostic marker for pancreatic cancer and is associated with its development. Thus, CCNI2 possesses potential to act as a therapeutic target for pancreatic cancer treatment.

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MiR-203a-3p Inhibits Pancreatic Cancer Cell Proliferation, EMT, and Apoptosis by Regulating SLUG

Technology in Cancer Research & Treatment ◽

10.1177/1533033819898729 ◽

2020 ◽

Vol 19 ◽

pp. 153303381989872 ◽

Cited By ~ 3

Author(s):

Ning An ◽

Bo Zheng

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Messenger Rnas ◽

Mesenchymal Transition ◽

Pancreatic Cancer Cells ◽

Cancer Tissues

Objective: The aim of the present research is to study the roles of miR-203a-3p on cell proliferation, migration, invasion, and epithelial–mesenchymal transition in pancreatic cancer. Methods: Transcription profiles were acquired from Gene Expression Omnibus database, which was used to screen out the differentially expressed microRNAs and messenger RNAs in pancreatic cancer. Pancreatic cancer tissues were used to verify the bioinformatics results by quantitative real-time polymerase chain reaction. The relationship between miR-203a-3p and SLUG was examined by TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation. The Cell Counting Kit-8, wound healing, and transwell assays were conducted to investigate the proliferation, migration, and invasion capability of pancreatic cancer cells, respectively. The expression of epithelial–mesenchymal transition–related proteins was determined by the Western blot assay. Xenograft assay was performed to verify findings from in vitro assays. Results: Bioinformatic analysis found that a total of 113 microRNAs and 1749 messenger RNAs expressed differentially in pancreatic cancer tissues. Among these microRNAs, the expression of miR-203a-3p was significantly decreased in both pancreatic cancer tissues and cells. On the other hand, the SLUG expression was remarkably upregulated in pancreatic cancer tissues and cells in comparison with normal tissues and cells. Moreover, TargetScan software, dual-luciferase reporter assay, and RNA immunoprecipitation revealed that SLUG was a target of miR-203a-3p. The upregulation of miR-203a-3p expression inhibited the proliferation, migration, and invasion ability of pancreatic cancer cells by suppressing the epithelial–mesenchymal transition process via sponging SLUG. Conclusion: These findings indicate that downregulation of miR-203a-3p in pancreatic cancer cells leads to high expression of SLUG, which promotes epithelial–mesenchymal transition process and induces cancer progression.

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Long non-coding RNA ZFAS1 promotes pancreatic cancer proliferation and metastasis by sponging miR-497-5p to regulate HMGA2 expression

Cell Death and Disease ◽

10.1038/s41419-021-04123-7 ◽

2021 ◽

Vol 12 (10) ◽

Author(s):

Min Rao ◽

Song Xu ◽

Yong Zhang ◽

Yifan Liu ◽

Wenkang Luan ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Biological Effects ◽

The Cancer Genome Atlas ◽

Luciferase Reporter ◽

Cancer Data ◽

Pancreatic Cancer Cells ◽

Cancer Tissues

AbstractThe lncRNA ZFAS1 plays a carcinogenic regulatory role in many human tumours, but it is rarely reported in pancreatic cancer. We identify the role and molecular mechanisms of ZFAS1 in pancreatic cancer. The expression of ZFAS1, miR-497-5p and HMGA2 in pancreatic cancer tissues was detected by qRT-PCR. Pancreatic cancer data in The Cancer Genome Atlas were also included in this study. CCK8, EdU, transwell and scratch wound assays were used to investigate the biological effects of ZFAS1 in pancreatic cancer cells. MS2-RIP, RNA pull-down, RNA-ChIP and luciferase reporter assays were used to clarify the molecular biological mechanisms of ZFAS1 in pancreatic cancer. The role of ZFAS1 in vivo was also confirmed via xenograft experiments. ZFAS1 was overexpressed in pancreatic cancer tissues. ZFAS1 promoted the growth and metastasis of pancreatic cancer cells, and miR-497-5p acted as a tumour suppressor gene in pancreatic cancer by targeting HMGA2. We also demonstrated that ZFAS1 exerts its effects by promoting HMGA2 expression through decoying miR-497-5p. We also found that ZFAS1 promoted the progression of pancreatic cancer in vivo by modulating the miR-497-5p/HMGA2 axis. In conclusion, this study revealed a new role for and the molecular mechanisms of ZFAS1 in pancreatic cancer, identifying ZFAS1 as a novel target for the diagnosis and treatment of pancreatic cancer.

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Increased levels of circulating circular RNA (hsa_circ_0013587) may serve as a novel biomarker for pancreatic cancer

Biomarkers in Medicine ◽

10.2217/bmm-2020-0750 ◽

2021 ◽

Author(s):

Kaiwei Xu ◽

Zhoujian Qiu ◽

Liu Xu ◽

Xuedan Qiu ◽

Lu Hong ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Diagnosis ◽

Circular Rna ◽

Circular Rnas ◽

Plasma Samples ◽

Qrt Pcr ◽

Reverse Transcription Pcr ◽

Pancreatic Cancer Cells ◽

Clinical Stages ◽

Cancer Tissues

Aim: Circular RNA can serve as a biomarker for early diagnosis of pancreatic cancer. Materials & methods: Analyzed the expression of various differentially expressed circular RNAs in the pancreatic cancer tissues by gene chip and identified the expression of hsa_circ_0013587 in pancreatic cancer cells, tissues and plasma by quantitative reverse transcription PCR (qRT-PCR). Results: Hsa_circ_0013587 was highly expressed in the pancreatic cancer tissues, cell lines and plasma samples from patients with pancreatic cancer. Notably, hsa_circ_0013587 was upregulated in pancreatic cancer patients with later clinical stages III–IV as compared with those detected in early clinical stages I–II. Conclusion: A high expression of hsa_circ_0013587 may serve as a novel diagnostic and therapeutic biomarker for pancreatic cancer.

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MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis

Frontiers in Oncology ◽

10.3389/fonc.2021.651535 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dan Zhang ◽

Zhiwei He ◽

Yiyi Shen ◽

Jie Wang ◽

Tao Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Glucose Metabolism ◽

Cell Lines ◽

Stress Responses ◽

Hot Spot ◽

Luciferase Reporter ◽

Proliferation And Metastasis ◽

Cancer Tissues

IntroductionMalignant proliferation and metastasis are some of the causes of high mortality in pancreatic cancer. MicroRNAs have been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. However, the biology function and underlying mechanism of miRNA regulating pancreatic cancer progress is remained uncleared.MethodsRNA-seq analysis the glycolysis associated miRNAs and verified miRNA-489-3p was involving in glycolysis. We used RNA in situ hybridization (ISH) and qRT-PCR to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues and cell lines. Then the function assay of in vivo and in vitro were used to evaluated the role of miR-489-3p in the proliferation, metastasis and glucose metabolism of pancreatic cancer. Furthermore, dual luciferase reporter and rescue experiments were performed to explore the mechanism underlying in the role of miRNA-489-3p.ResultsWe determined that glycolysis associated miRNA miR-489-3p was downregulated in pancreatic cancer tissues and cell lines. The gain and loos of function experiments confirmed that miR-489-3p could inhibit the proliferation, metastasis and glucose metabolism of pancreatic cancer. Further, we found that miR-489-3p could target regulating LDHA and PKM through the luciferase report experiment. Finally, in vivo experiment confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.ConclusionIn short, this study identified miR-489-3p as a novel therapy target for pancreatic cancer which was involving in the proliferation, metastasis and glycolysis, but its diagnostic value deserves further study.

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