MicroRNA-148a Suppresses the Proliferation and Migration of Pancreatic Cancer Cells by Down-regulating ErbB3

Feng, Hui; Wang, Yalei; Su, Jiaojiao; Liang, Hongwei; Zhang, Chenyu; Chen, Xi; Yao, Weiyan

doi:10.1097/mpa.0000000000000677

Cited by 27 publications

(27 citation statements)

References 31 publications

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“…Most analyses have focused on guide strands of the miR‐148 ‐family in normal physiological conditions or in cancer cells . A large number of previous studies showed that miR‐148a‐3p (the guide strand) was downregulated in several types of cancer (eg, gastric cancer, colon cancer, hepatocellular carcinoma, breast cancer and PDAC) . The miR‐148a gene contains a large number of CpG islands in the promoter (Figure A).…”

Section: Discussionmentioning

confidence: 99%

“…30,31 A large number of previous studies showed that miR-148a-3p (the guide strand) was downregulated in several types of cancer (eg, gastric cancer, colon cancer, hepatocellular carcinoma, breast cancer and PDAC). [32][33][34][35][36] The miR-148a gene contains a large number of CpG islands in the promoter ( Figure S3A). In hepatocellular cancer, miR-148a is silenced by DNA hypermethylation.…”

Section: Discussionmentioning

confidence: 99%

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Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

et al. 2018

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We previously used RNA sequencing to establish the microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands of pre‐miR‐148a (miR‐148a‐5p: the passenger strand and miR‐148a‐3p: the guide strand) were downregulated in cancer tissues. Ectopic expression of miR‐148a‐5p and miR‐148a‐3p significantly inhibited cancer cell migration and invasion, indicating that both strands of pre‐miR‐148a had tumor‐suppressive roles in PDAC cells. In silico database and genome‐wide gene expression analyses identified a total of 15 genes that were putative targets regulated by these miRNAs. High expression of miR‐148a‐5p targets (PHLDA2,LPCAT2 and AP1S3) and miR‐148a‐3p targets (SMA, ENDOD1 and UHMK1) was associated with poor prognosis of patients with PDAC. Moreover, knockdown of PHLDA2 expression inhibited cancer cell aggressiveness, suggesting PHLDA2 acted as an oncogene in PDAC cells. Involvement of the passenger strand of pre‐miR‐148a (miR‐148‐5p) is a new concept in cancer research. Novel approaches that identify tumor‐suppressive miRNA regulatory networks in lethal PDAC might provide new prognostic markers and therapeutic targets for this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

et al. 2018

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“…miR-148a has been identified as a tumor suppressor miRNA in several types of cancer (5)(6)(7)(8)(9); however, the antitumor effects of miR-148a remain controversial in pancreatic cancer. At least four studies have revealed that re-expression of miR-148a inhibits cell proliferation, apoptosis, migration and invasion in pancreatic cancer (12)(13)(14)(15). However, Delpu et al (35) demonstrated that miR-148a does not impact PDAC proliferation in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…miR-148a is also downregulated in pancreatic cancer tissues and several pancreatic cell lines (10,11). In addition, DNA methyltransferase 1 (DNMT1) (12), cholecystokinin b receptor (13), b-cell lymphoma 2 (13), cell division cycle 25b (14) and erb-b2 receptor tyrosine kinase 3 (15) have been identified as target genes of miR-148a. DNA methylation is one of the epigenetic mechanisms affecting cell fate via the regulation of gene expression.…”

Section: The Interaction Between Mir-148a and Dnmt1 Suppresses Cell Mmentioning

confidence: 99%

The interaction between miR‑148a and DNMT1 suppresses cell migration and invasion by reactivating tumor suppressor genes in pancreatic cancer

et al. 2018

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DNA methylation is an epigenetic mechanism that cells use to control gene expression, which serves an important role in tumorigenesis. DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of the pattern of DNA methylation. Overexpression of DNMT1 is observed in numerous malignant tumors, including pancreatic cancer, and results in silencing of several key tumor suppressor genes (TSGs). Recent studies have suggested that microRNAs (miRNAs/miRs) contribute to the regulation of DNMT1 expression, and promoter hypermethylation caused by DNMT1 overexpression is associated with the dysfunction of some miRNAs. The present study aimed to reveal the interaction between miR‑148a and DNMT1, and its effects on cell proliferation, migration and invasion of pancreatic cancer cells. Initially, the expression levels of DNMT1 and miR‑148a were detected in pancreatic cancer tissues and AsPC‑1 cells by reverse transcription‑quantitative polymerase chain reaction (PCR). Secondly, the regulatory effects of DNMT1 on miR‑148a were evaluated using methylation‑specific PCR. Furthermore, bioinformatics analysis and dual luciferase reporter assay were used to verify the target relationship between miR‑148a and DNMT1. Finally, in vitro rescue experiments were conducted to evaluate the effects of miR‑148a on the expression of TSGs and the malignant phenotype in AsPC‑1 cells. The results demonstrated that DNMT1 was aberrantly upregulated in pancreatic cancer, and was responsible for hypermethylation of the miR‑148a promoter. Furthermore, DNMT1 was revealed as a direct target of miR‑148a by dual luciferase reporter assay, and restoration of miR‑148a could reactivate TSGs, such as p16, preproenkephalin and Ras association domain family member 1 by targeting DNMT1 in the AsPC‑1 pancreatic cancer cell line. These results indicated that an interaction exists between miR‑148a and DNMT1 in pancreatic cancer. Notably, miR‑148a overexpression significantly inhibited cell proliferation, migration and invasion in AsPC‑1 cells. Therefore, miR‑148a may serve as a novel therapeutic target for the treatment of pancreatic cancer.

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“…Moreover, positive correlation was detected for downregulation of tumor suppressing miRNAs miR-148a and miR-217 ( Table 5). Both of them inhibit cell proliferation [52,53], therefore it may be necessary to deactivate them in tumors for successful cancerogenesis. Additionally, positive correlation was detected for downregulation of tumor suppressing miRNAs miR-96 and miR-196a (Table 5).…”

Section: Discussionmentioning

confidence: 99%

Expression of selected MicroRNAs in pancreatic ductal adenocarcinoma in relation to tumor progression and patient’s outcome.

Popov

Szabó²,

Gürlich³

et al. 2019

Preprint

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Background: pancreatic ductal adenocarcinoma (PDAC) remains a disease with extremely poor prognosis and limited effective available treatment. Differential expression of miRNAs isolated from tumor tissue has been proposed as a marker for tumor diagnosis, progression and prognosis. Nevertheless, prognostic value of miRNAs expression in PDACs for patient outcome still remains unclear.Methods: expression of 7 selected miRNAs, isolated from FFPE samples of 54 PDAC patients, was quantified using RT-qPCR. The relationship of miRNA expression levels with tumor histology, clinico-pathological characteristics, patient overall survival (OS) and progress-free survival (PFS), was subsequently evaluated.Results: overexpression of miR-21, miR-155 and miR-210 was observed in PDACs (up to 72.62-fold, 232.36 and 181.38-fold respectively), in comparison with non-neoplastic tissues. On the other hand, miR-96 and miR-217 were significantly downregulated in PDACs (up to one hundred times). No differences were, however, noticed between cancer and normal tissues for the expression levels of miR-148a and miR-196a.On the other hand, expression levels of all 7 miRNAs failed to demonstrate significant correlation with parameters of tumor progression, such as tumor stage, grade, nodal involvement, perineural and vascular invasion. Positive correlation of miR-210 levels was, however, observed with patient age (ρ=0.35). Additionally, miR-148a and miR-217 expression have shown positive association with tubular tumor growth pattern (ρ=0.39; ρ=0.28). Negative correlation of miR-148a values was also demonstrated with dissociative growth pattern and nuclear atypia (ρ=-0.30; ρ=0.27).

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MicroRNA-148a Suppresses the Proliferation and Migration of Pancreatic Cancer Cells by Down-regulating ErbB3

Abstract: Taken together, the present study provides the first evidence that miR-148a plays a significant role in the suppression of pancreatic tumorigenesis via the inhibition of ErbB3 translation.

Cited by 27 publications

References 31 publications

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

The interaction between miR‑148a and DNMT1 suppresses cell migration and invasion by reactivating tumor suppressor genes in pancreatic cancer

Expression of selected MicroRNAs in pancreatic ductal adenocarcinoma in relation to tumor progression and patient’s outcome.

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