Prognostic relevance of miR‐137 in patients with hepatocellular carcinoma

Sakabe, Tomohiko; Azumi, Junya; Umekita, Yoshihisa; Toriguchi, Kan; Hatano, Etsuro; Hirooka, Yasuaki; Shiota, Goshi

doi:10.1111/liv.13213

Cited by 23 publications

(28 citation statements)

References 54 publications

(99 reference statements)

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“…Furthermore, transwell assays clearly showed that the overexpression of miR-137 promotes the invasion and metastasis of Bel-7402 and Huh-7 cells (Figure 6e). (Sakabe et al, 2017). Our findings from a significantly higher number of 375 HCC patients are consistent with that study.…”

Section: In Vitro Validation Of Afm As a Target Gene Of Mir-137 Andsupporting

confidence: 92%

Prognostic relevance of miR‐137 and its liver microenvironment regulatory target gene AFM in hepatocellular carcinoma

Qian

Zhao

Jiang

et al. 2018

Journal Cellular Physiology

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MiR‐137 has been identified as potential hepatocellular carcinoma (HCC) prognostic biomarkers. Highly relevant HCC prognostic biomarkers may be derived from combinations of miR‐137 with its target genes involved in the regulation of liver microenvironment. This study aimed at the discovery of such a combination with improved HCC prognosis performance than miR‐137 or its target gene alone in a significantly higher number of HCC patients than previous studies. Analysis of the differentially expressed micro RNAs (miRNAs) between cancer and noncancer tissues reconfirmed miR‐137 to be among the most relevant prognostic miRNAs and the data of 375 HCC patients and 50 normal cases were from the Cancer Genome Atlas (TCGA) data sets. Target genes were identified by the established search methods and Kaplan–Meier survival analysis of HCC patients was used to evaluate the overall survival (OS) and recurrence‐free survival (RFS). Cox proportional hazards regression indicated that the miR‐137 and its target gene AFM combination is an independent prognostic factor for the OS and RFS in HCC. In vitro experiments validated that miR‐137 could bind to 3′‐untranslated region of the AFM and promote the invasion and metastasis of HCC cell lines. The expressions of miR‐137 and its liver microenvironment regulatory target gene AFM in combination significantly correlated with HCC progression in a higher number of patients than in previous studies, which suggested their potential as prognostic biomarkers for HCC.

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Section: In Vitro Validation Of Afm As a Target Gene Of Mir-137 Andsupporting

confidence: 92%

Prognostic relevance of miR‐137 and its liver microenvironment regulatory target gene AFM in hepatocellular carcinoma

Qian

Zhao

Jiang

et al. 2018

Journal Cellular Physiology

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“…Representative images of sphere formation in CD44-positive and -negative cells treated with DMSO, 5-FU, PNU74654, IC-2, and PN-3-13 were shown in Figure 4A. The sphere-forming ability of CD44-positive DMSO-treated cells, was higher than that of CD44-negative cells, as previously reported (4). Less sphere formation and smaller spheres were found in cells treated with 5-FU, PNR74654, IC-2 and PN-3-13 ( Figure 4A).…”

Section: Effect Of Small-molecule Compounds On Sphere-forming Abilitysupporting

confidence: 81%

“…Flow cytometry. Flow cytometric analysis was performed as previously reported (4). HCC cell lines were treated with smallmolecule compounds for 48 h. After incubation, harvested cells were incubated with blocking solution containing 0.5% bovine serum albumin, 0.5% FBS, and 2 mM EDTA for 15 min at 4˚C.…”

Section: Methodsmentioning

confidence: 99%

“…Sphere-formation assay. The sphere-forming ability of cancer cells was determined as previously reported (4) . The CD44-positive and CD44-negative cells fractions from HuH7 cells (5.0×10 4 cells/well) were seeded onto ultra-low attachment 24-well plate (Corning, Corning, NY, USA), and cultured in DMEM/Nutrient Mixture F-12 Ham (DMEM/F12; Sigma-Aldrich, MO, USA) containing 20 ng/ml human recombinant epidermal growth factor (EGF), 20 ng/ml human recombinant basic fibroblast growth factor (bFGF), 1 × B27 supplement (Gibco, Life Technologies Corp.), and L-glutamine for 24 h. After incubation, cells were treated with 1% DMSO, 0.5 μM 5-FU, 5 μM ionomycin, 200 μM PNU74654, 50 μM IC-2, and 10 μM PN-3-13, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The aberrant differentiation into various types of cancer cells from CSCs provides a mechanism for generating phenotypic and functional tumor heterogeneity (1). In addition, we reported that the presence of CSCs serves as a prognostic marker for overall survival in patients with hepatocellular carcinoma (HCC), suggesting that undifferentiated CSCs are responsible for tumor growth and disease progression (4). Recent studies suggested the existence of an intimate relationship between liver stem cells and primary liver cancer according to the following CSC hypothesis.…”

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confidence: 99%

See 2 more Smart Citations

A Novel Small-molecule WNT Inhibitor, IC-2, Has the Potential to Suppress Liver Cancer Stem Cells

Seto

Sakabe

Itaba

et al. 2017

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Suppression of intrahepatic cholangiocarcinoma cell growth by SKI via upregulation of the CDK inhibitor p21

et al. 2022

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Cholangiocarcinoma (CC) has a poor prognosis and different driver genes depending on the site of onset. Intrahepatic CC is the second-most common liver cancer after hepatocellular carcinoma, and novel therapeutic targets are urgently needed. The present study was conducted to identify novel therapeutic targets by exploring differentially regulated genes in human CC. MicroRNA (miRNA) and mRNA microarrays were performed using tissue and serum samples obtained from 24 surgically resected hepatobiliary tumor cases, including 10 CC cases. We conducted principal component analysis to identify differentially expressed miRNA, leading to the identification of miRNA-3648 as a differentially expressed miRNA. We used an in silico screening approach to identify its target mRNA, the tumor suppressor Sloan Kettering Institute (SKI). SKI protein expression was decreased in human CC cells overexpressing miRNA-3648, endogenous SKI protein expression was decreased in human CC tumor tissues, and endogenous SKI mRNA expression was suppressed in human CC cells characterized by rapid growth. SKI-overexpressing OZ cells (human intrahepatic CC cells) showed upregulation of cyclin-dependent kinase inhibitor p21 mRNA and protein expression and suppressed cell proliferation. Nuclear expression of CDT1 (chromatin licensing and DNA replication factor 1), which is required for the G1/S transition, was suppressed in SKI-overexpressing OZ cells. SKI knockdown resulted in the opposite effects. Transgenic p21-luciferase was activated in SKI-overexpressing OZ cells. These data indicate SKI involvement in p21 transcription and that SKI-p21 signaling causes cell cycle arrest in G1, suppressing intrahepatic CC cell growth. Therefore, SKI may be a potential therapeutic target for intrahepatic CC.

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Prognostic relevance of miR‐137 in patients with hepatocellular carcinoma

Abstract: miR-137 may serve as a prognostic marker in patients with HCC and may be a potential target for the elimination of liver CSCs.

Cited by 23 publications

References 54 publications

Prognostic relevance of miR‐137 and its liver microenvironment regulatory target gene AFM in hepatocellular carcinoma

Prognostic relevance of miR‐137 and its liver microenvironment regulatory target gene AFM in hepatocellular carcinoma

A Novel Small-molecule WNT Inhibitor, IC-2, Has the Potential to Suppress Liver Cancer Stem Cells

Suppression of intrahepatic cholangiocarcinoma cell growth by SKI via upregulation of the CDK inhibitor p21

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