Hsa-miR-137, hsa-miR-520e and hsa-miR-590-3p perform crucial roles in Lynch syndrome

Zhou, Chunyuan; Li, Jiayu; Li, Jiarui; Wan, Yingchun; Li, Tao; Ma, Piyong; Wang, Yingjian; Sang, Haiyan

doi:10.3892/ol.2016.4816

Cited by 12 publications

(15 citation statements)

References 54 publications

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“…Our data suggested miR-137 controlled MSH2 expression via the 3′UTR, and its dysregulation putatively promoted tumorigenesis in colon cells. Recently, Zhou et al reported the role of miR-137 in LS tumor pathogenesis [ 33 ], potentially reinforcing our hypothesis that MSH2 is targeted by miR-137.…”

Section: Discussionsupporting

confidence: 87%

MiR-137 Targets the 3′ Untranslated Region of MSH2: Potential Implications in Lynch Syndrome-Related Colorectal Cancer

Liccardo

Sessa

Trombetti

et al. 2021

Cancers

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Mismatch Repair (MMR) gene dysregulation plays a fundamental role in Lynch Syndrome (LS) pathogenesis, a form of hereditary colorectal cancer. Loss or overexpression of key MMR genes leads to genome instability and tumorigenesis; however, the mechanisms controlling MMR gene expression are unknown. One such gene, MSH2, exerts an important role, not only in MMR, but also in cell proliferation, apoptosis, and cell cycle control. In this study, we explored the functions and underlying molecular mechanisms of increased MSH2 expression related to a c.*226A>G variant in the 3′untranslated (UTR) region of MSH2 that had been previously identified in a subject clinically suspected of LS. Bioinformatics identified a putative binding site for miR-137 in this region. To verify miRNA targeting specificity, we performed luciferase gene reporter assays using a MSH2 3′UTR psiCHECK-2 vector in human SW480 cells over-expressing miR-137, which showed a drastic reduction in luciferase activity (p > 0.0001). This effect was abolished by site-directed mutagenesis of the putative miR-137 seed site. Moreover, in these cells we observed that miR-137 levels were inversely correlated with MSH2 expression levels. These results were confirmed by results in normal and tumoral tissues from the patient carrying the 3′UTR c.*226A>G variant in MSH2. Finally, miR-137 overexpression in SW480 cells significantly suppressed cell proliferation in a time- and dose-dependent manner (p < 0.0001), supporting a role for MSH2 in apoptosis and cell proliferation processes. Our findings suggest miR-137 helps control MSH2 expression via its 3′UTR and that dysregulation of this mechanism appears to promote tumorigenesis in colon cells.

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Section: Discussionsupporting

confidence: 87%

MiR-137 Targets the 3′ Untranslated Region of MSH2: Potential Implications in Lynch Syndrome-Related Colorectal Cancer

Liccardo

Sessa

Trombetti

et al. 2021

Cancers

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“…Balaguer et al have shown that miRs can be used in tumor classification and discrimination of sporadic and hereditary tumors with microsatellite instability (14), thus highlighting the potential role of miRs as LS biomarkers. In support, Valeri et al, Liccardo et al and Zhou et al postulated that miRs could have functional roles in LS carcinogenesis, e.g., by targeting MMR-proteins (15,16) and various tumor-suppressor genes (17). However, these studies along with other reports have assessed miR functions in the colorectum and colorectal cancer tissues and cells as well as with microarray data in silico (14)(15)(16)(17)(18)(19) but not in circulation.…”

Section: Introductionmentioning

confidence: 94%

Systemic circulating microRNA landscape in Lynch syndrome

Sievänen

Korhonen

Jokela

et al. 2022

Preprint

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MicroRNAs (miRs) are non-coding RNA-molecules that regulate gene expression. Global circulating miR (c-miR) expression patterns (c-miRnome) change with carcinogenesis in various sporadic cancers. Therefore, aberrantly expressed c-miRs could have diagnostic, predictive and prognostic potential in molecular profiling of cancers. c-miR functions in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), also known as Lynch syndrome (LS), have remained understudied. LS cohort provides an ideal population for biomarker mining due to increased lifelong cancer risk and excessive cancer occurrence. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers. Our discovery cohort included 81 healthy path_MMR carriers and 37 non-LS controls. Our analysis also included cancer cohort comprised of 13 path_MMR carriers with varying cancers and 24 sporadic rectal cancer patients. We showed for the first time that c-miRnome can discern healthy path_MMR carriers from non-LS controls but does not distinguish healthy path_MMR carriers from cancer patients with or without path_MMR. Our c-miR expression analysis combined with in silico tools suggest ongoing alterations of biological pathways shared in LS and sporadic carcinogenesis. We observed that these alterations can produce a c-miR signature which can be used to track oncogenic stress in cancer-free path_MMR carriers. Thus, c-miRs hold potential in monitoring which cancer patients would require more intensive surveillance or clinical management.

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“…Hsa-miR-590-3p is one of the mature members of the human microRNA-590 family. It has been reported that miR-590-3p is related to the development of several kinds of cancer, including colorectal cancer (CRC), 6 Lynch syndrome (a common hereditary form of CRC), 7 glioblastoma 8 and nephroblastoma. 9 However, the effect of miR-590-3p in PC cells has not been reported to our knowledge.…”

Section: Introductionmentioning

confidence: 99%

<p><em>Hsa-MiR-590-3p</em> Promotes the Malignancy Progression of Pancreatic Ductal Carcinoma by Inhibiting the Expression of p27 and PPP2R2A via G1/S Cell Cycle Pathway</p>

Shi¹,

Sheng²,

Chen³

et al. 2020

OTT

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Objective To investigate the effect of miR-590-3p on the malignant biological behavior of pancreatic cancer, and to explore the target genes and pathways directly affected by miR-590-3p , to provide new therapeutic ideas and targets for the study of the diagnosis and treatment of pancreatic cancer. Methods We used qRT-PCR to measure miR-590-3p expression quantities. We used cell cycle, CCK-8, clonal formation to verify the change of proliferation capacity of PC cells. We used transwell assay to detect the migration and invasion of PC cells. We used the bioinformatics tool TargetScan ( http://www.targetscan.org ) to identify the possible target genes of miR-590-3p . Immunohistochemistry revealed the clinicopathological significance of PPP2R2A, p27 and miR-590-3p in the expression of pancreatic cancer. Western blot was used to detect the expression changes of PPP2R2A, p27 and G1/S cell cycle pathway-related proteins CDK2, cyclinE2 and p21 after transfection of mimics and inhibitors of miR-590-3p. Results According to our study, hsa-miR-590-3p expression was significantly higher in PC tissues than that in paired normal pancreas, which was associated with PC tumor size ( P =0.042) and preoperative CA19-9 level ( P =0.046) of PC patients. Its overexpression promoted PC cell proliferation, invasion and migration following with the p27 and PPP2R2A protein downregulation in Capan-2, PANC-1 and BxPC-3 cells, and vice versa. Bioinformatics analysis and dual-luciferase reporter assay further confirmed that p27 and PPP2R2A were direct target genes of miR-590-3p . The negative relationship of miR-590-3p with p27 and PPP2R2A was also observed in PC tissues. Conclusion MiR-590-3p promotes the proliferation, migration and invasion of pancreatic cancer cells. MiR-590-3p directly downregulated p27 and PPP2R2A and via the G1/S cell cycle pathway to promote the development of pancreatic cancer.

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Hsa-miR-137, hsa-miR-520e and hsa-miR-590-3p perform crucial roles in Lynch syndrome

Cited by 12 publications

References 54 publications

MiR-137 Targets the 3′ Untranslated Region of MSH2: Potential Implications in Lynch Syndrome-Related Colorectal Cancer

MiR-137 Targets the 3′ Untranslated Region of MSH2: Potential Implications in Lynch Syndrome-Related Colorectal Cancer

Systemic circulating microRNA landscape in Lynch syndrome

<p><em>Hsa-MiR-590-3p</em> Promotes the Malignancy Progression of Pancreatic Ductal Carcinoma by Inhibiting the Expression of p27 and PPP2R2A via G1/S Cell Cycle Pathway</p>

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