Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma

Moshiri, Farzaneh; Salvi, Alessandro; Gramantieri, Laura; Sangiovanni, A.; Guerriero, Paola; Petro, Giuseppina De; Bassi, Cristian; Lupini, Laura; Sattari, Arash; Cheung, Douglas G.; Veneziano, Dario; Nigita, Giovanni; Shankaraiah, Ram C.; Portolani, Nazario; Carcoforo, Paolo; Fornari, Francesca; Bolondi, Luigi; Frassoldati, Antonio; Sabbioni, Silvia; Colombo, Massimo; Croce, Carlo M.; Negrini, Massimo

doi:10.18632/oncotarget.24601

Cited by 80 publications

(67 citation statements)

References 63 publications

(67 reference statements)

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“…Thus, our results fit a model of translational suppression by AML-EV miRNA [64] and find support in existing reports of miRNA suppression of protein synthesis [65,66] and Raptor deregulation in hematopoietic cells [67][68][69]. Although miR-1246 was previously identified as a regulator of cancer progression, drug resistance [70,71], and a putative biomarker [31,72], our data suggest a role in regulating other tissue compartments, including BM HSC.…”

Section: Discussionsupporting

confidence: 90%

“…Moreover, Raptor was previously shown to be required for HSC regeneration and its loss led to accumulation of monocytoid cells, pancytopenia, and splenomegaly in mice [63]. Although miR-1246 was previously identified as a regulator of cancer progression, drug resistance [70,71], and a putative biomarker [31,72], our data suggest a role in regulating other tissue compartments, including BM HSC. Thus, our results fit a model of translational suppression by AML-EV miRNA [64] and find support in existing reports of miRNA suppression of protein synthesis [65,66] and Raptor deregulation in hematopoietic cells [67][68][69].…”

Section: Discussionmentioning

confidence: 61%

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Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

et al. 2019

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Progressive remodeling of the bone marrow microenvironment is recognized as an integral aspect of leukemogenesis. Expanding acute myeloid leukemia (AML) clones not only alter stroma composition, but also actively constrain hematopoiesis, representing a significant source of patient morbidity and mortality. Recent studies revealed the surprising resistance of long‐term hematopoietic stem cells (LT‐HSC) to elimination from the leukemic niche. Here, we examine the fate and function of residual LT‐HSC in the BM of murine xenografts with emphasis on the role of AML‐derived extracellular vesicles (EV). AML‐EV rapidly enter HSC, and their trafficking elicits protein synthesis suppression and LT‐HSC quiescence. Mechanistically, AML‐EV transfer a panel of miRNA, including miR‐1246, that target the mTOR subunit Raptor, causing ribosomal protein S6 hypo‐phosphorylation, which in turn impairs protein synthesis in LT‐HSC. While HSC functionally recover from quiescence upon transplantation to an AML‐naive environment, they maintain relative gains in repopulation capacity. These phenotypic changes are accompanied by DNA double‐strand breaks and evidence of a sustained DNA‐damage response. In sum, AML‐EV contribute to niche‐dependent, reversible quiescence and elicit persisting DNA damage in LT‐HSC.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 61%

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

et al. 2019

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“…Moshiri et al . reported the clinical utility of miR‐1246 as a plasma, but not serum, diagnostic biomarker of HCC . However, Wang et al .…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Chuma

Toyoda

Matsuzaki³

et al. 2019

Hepatology Research

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Aims Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real‐time quantitative reverse transcription–polymerase chain reaction (PCR). Results Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA‐1246 (miR‐1246). Quantitative PCR confirmed that miR‐1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR‐1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR‐1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR‐1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528–5.071; P = 0.0008). Conclusion Circulating miR‐1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

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“…In addition, they have the potential to serve as biomarkers for the diagnosis, staging, progression, and prognosis of cancer . This is evident from several published reports that have shown the use of circulating miRNAs in early cancer detection, such as miR‐196a in gastric cancer, and the diagnostic roles of miR‐106b‐3p, miR‐101‐3p, and miR‐1246 in hepatocellular carcinoma . In lung cancer, low expression of the circulating miRNA‐34 family was associated with clinicopathological status and poor progression‐free and overall survival of NSCLC patients .…”

Section: Introductionmentioning

confidence: 98%

“…15 This is evident from several published reports that have shown the use of circulating miRNAs in early cancer detection, such as miR-196a in gastric cancer, 16 and the diagnostic roles of miR-106b-3p, miR-101-3p, and miR-1246 in hepatocellular carcinoma. 17 In lung cancer, low expression of the circulating miRNA-34 family was associated with clinicopathological status and poor progression-free and overall survival of NSCLC patients. 18 miR-223, miR-20a, miR-448, and miR-145, as serum/plasma miRNA signatures, have shown high sensitivity (>80%), whereas another panel including miR-628-3p, miR-29c, miR-210, and miR-1244 have shown high specificity (>90%) to stage I-II NSCLC samples.…”

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confidence: 99%

Circulating microRNA‐590‐5p functions as a liquid biopsy marker in non‐small cell lung cancer

et al. 2020

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Despite the availability of various diagnostic procedures, a tissue biopsy is still indispensable for the routine diagnosis of lung cancer. However, inaccurate diagnoses can occur, leading to inefficient cancer management. In this context, use of circulating microRNAs (miRNAs) may serve as diagnostic tools as liquid biopsies, and as biomarkers to better understand the molecular mechanisms involved in the progression of cancer. We identified miR‐590‐5p as a potential prognostic marker in the progression of non‐small cell lung cancer (NSCLC). We were able to detect this miRNA in blood plasma samples of NSCLC patients through quantitative real‐time PCR. Our data showed an ~7.5‐fold downregulation of miR‐590‐5p in NSCLC patients compared to healthy controls, which correlated with several clinicopathological features. Further, overexpression of miR‐590‐5p led to decreased cell viability, proliferation, colony formation, migration, and invasion potential of lung cancer cells, whereas its knockdown showed the opposite effect. In addition, the levels of several proteins involved in the epithelial‐to‐mesenchymal transition negatively correlated with miR‐590‐5p levels in lung adenocarcinoma cells and tumors of NSCLC patients. Further, dual‐luciferase reporter assays identified STAT3 as a direct target of miR‐590‐5p, which negatively regulated STAT3 activation and its downstream signaling molecules (eg, Cyclin D1, c‐Myc, Vimentin, and β‐catenin) involved in tumorigenesis. Taken together, our study suggests that miR‐590‐5p functions as a tumor suppressor in NSCLC through regulating the STAT3 pathway, and may serve as a useful biomarker for the diagnosis/prognosis of NSCLC, and as a potential therapeutic target for the treatment of NSCLC.

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Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma

Cited by 80 publications

References 63 publications

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Circulating microRNA‐590‐5p functions as a liquid biopsy marker in non‐small cell lung cancer

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