The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors

Gyvyte, Ugne; Lukoševičius, Rokas; Inčiūraitė, Rūta; Streleckiene, Greta; Gudoitytė, Greta; Bekampytė, Justina; Valentini, Serena; Šaltenienė, Violeta; Ruzgys, Paulius; Šatkauskas, Saulius; Žvinienė, Kristina; Kupčinskas, Juozas; Skiecevičienė, Jurgita

doi:10.3390/ijms21145151

Cited by 14 publications

(15 citation statements)

References 45 publications

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“…A previously well-established workflow for dual luciferase assay using AGS cells was applied for this experiment [57,58]. Cells were co-transfected with hsa-miR-1246 mimic and miR-Control, pMIR-REPORT-Luciferase-WT vector, pMIR-REPORT-Luciferase-MT vector, and pMIR-REPORT-ß-galactosidase control vector (Invitrogen, Carlsbad, CA, USA).…”

Section: Dual Light Luciferase Assaymentioning

confidence: 99%

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

Lukoševičius

Juzėnas

Šaltenienė

et al. 2022

IJMS

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Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes’ expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.

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Section: Dual Light Luciferase Assaymentioning

confidence: 99%

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

Lukoševičius

Juzėnas

Šaltenienė

et al. 2022

IJMS

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“…Concerned to liver cancer, up‐regulated miR‐375 repressed cell growth via interacting with the downstream gene ErbB2 29 . In gastrointestinal stromal tumour, overexpressed miR‐375‐3p attenuated cell viability and migration rate 30 . In our study, miR‐375 was found to be sponged by circASPH and target MAP2K6, and the silencing of miR‐375 restrained PCOS development by interacting with circASPH.…”

Section: Discussionmentioning

confidence: 47%

CircASPH promotes KGN cells proliferation through miR‐375/MAP2K6 axis in Polycystic Ovary Syndrome

Xia

Yang

et al. 2020

J Cellular Molecular Medi

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Polycystic Ovary Syndrome (PCOS) is a kind of endocrine disorder which is prevalent in adult women, so exploring more biomarkers for PCOS is imperative. Recently, circular RNA and microRNA are confirmed to be related with PCOS development. Whether circular RNA ASPH (circASPH) is involved in PCOS need to be studied further. We utilized RT‐qPCR to measure the expression levels of circASPH, miR‐375 and MAP2K6 in PCOS patients and normal group. The effects of circASPH and miR‐375 on KGN cells proliferation and apoptosis were observed by CCK‐8 assay, EdU incorporation assay and apoptosis assay, separately. Then Dual‐luciferase reporter assay was carried out to verify the circASPH/miR375 axis and miR375/MAP2K6 axis. The interaction between circASPH and MAP2K6 were detected with the support of RT‐qPCR and Western blot. We found circASPH and MAP2K6 were both over‐expressed in PCOS patients, while miR‐375 was in the opposite direction. Moreover, miR‐375 was negatively regulated by circASPH, while MAP2K6 was positively regulated by circASPH. In addition, circASPH directly targeted miR‐375, which targeted MAP2K6. More than that, the knockdown of circASPH repressed KGN cells proliferation and enhanced apoptosis, while the silence of miR‐375 reversed the above effects. In conclusion, circASPH promotes KGN cells proliferation through miR‐375/MAP2K6 axis in PCOS, and they are thought‐provoking biomarkers for PCOS diagnosis and therapy.

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“…It was found that miR-215-5p levels were negatively correlated with the risk-grade of GIST and that miR-509-3p is upregulated in epitheloid and mixed cell type GIST compared to the spindle type. In a subsequent study the same group focused on miR-200b-3p and miR-375-3p-both were found to be reduced in GIST compared to normal adjacent tissue [91]. These miRNAs negatively affected cell viability and cellular migratory capability when overexpressed in GIST-T1 cells.…”

Section: Dysregulated Mirnas In Gistmentioning

confidence: 94%

“…Enhanced expression of miR-222 in GIST cells by miRNA mimics inhibited cell proliferation, affected cell cycle progression and induced apoptosis [88]. Additionally, miR-218 and miR-375-3p were mentioned to regulate KIT as well as miR-494, an miRNA associated with 14q loss [90][91][92]. The transient modulation of miR-494 in the GIST882 cell line led to inverse responses in KIT protein levels.…”

Section: Dysregulated Mirnas In Gistmentioning

confidence: 99%

Non-Coding RNAs, a Novel Paradigm for the Management of Gastrointestinal Stromal Tumors

Amirnasr

Sleijfer

Wiemer

2020

IJMS

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies found in the gastrointestinal tract. At a molecular level, most GISTs are characterized by gain-of-function mutations in V-Kit Hardy–Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog (KIT) and Platelet Derived Growth Factor Receptor Alpha (PDGFRA), leading to constitutive activated signaling through these receptor tyrosine kinases, which drive GIST pathogenesis. In addition to surgery, treatment with the tyrosine kinase inhibitor imatinib forms the mainstay of GIST treatment, particularly in the advanced setting. Nevertheless, the majority of GISTs develop imatinib resistance. Biomarkers that indicate metastasis, drug resistance and disease progression early on could be of great clinical value. Likewise, novel treatment strategies that overcome resistance mechanisms are equally needed. Non-coding RNAs, particularly microRNAs, can be employed as diagnostic, prognostic or predictive biomarkers and have therapeutic potential. Here we review which non-coding RNAs are deregulated in GISTs, whether they can be linked to specific clinicopathological features and discuss how they can be used to improve the clinical management of GISTs.

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The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors

Cited by 14 publications

References 45 publications

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

CircASPH promotes KGN cells proliferation through miR‐375/MAP2K6 axis in Polycystic Ovary Syndrome

Non-Coding RNAs, a Novel Paradigm for the Management of Gastrointestinal Stromal Tumors

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