miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma

Zhou, Shuguang; Wang, Bing; Hu, Jun; Zhou, Yucheng; Jiang, Mengzhen; Wu, Mingyu; Qin, Liqiang; Yang, Xuming

doi:10.1007/s13277-015-4578-5

Cited by 53 publications

(49 citation statements)

References 47 publications

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“…MicroRNA-421 (miR-421) is a molecule that has been studied extensively. It has been investigated and found to be expressed aberrantly in various types of cancer (Li et al 2018;Wang et al 2018;Zhou et al 2016). Previous studies showed that miR-421 rises notably in tissue and gastric juice, as well as in blood mononuclear cells and serum of gastric cancer (Liu et al 2015;Zhang et al 2012a;Zhao et al 2015), suggesting that miR-421 seems to be an ideal biomarker for gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

Peer Review #2 of "Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer (v0.2)"

2019

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MicroRNA (miR)-421 plays a key role in cancer progression. It has been reported that circulating miR-421may be a potential tumor marker for the diagnosis of several cancers. However, the role of miR-421 in plasma as a potential biomarker in the diagnosis of precancerous gastric lesions (Pre) and early-stage gastric cancer (GC) remains poorly understood. In this study, we investigated miR-421 in plasma as a novel potential biomarker for the detection of precancerous gastric lesions and early-stage (GC). Materials & Methods. The miRNA content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-421 content in all subjects was normalized by endogenous miRNA (miR-16). The diagnostic value of miR-421 for Pre and GC was assessed by comparing receiver operating characteristic (ROC) analysis with traditional tumor markers, including CEA, CA125, CA153, CA211 and CA50. The correlation between the expression of miR-421 and the pathological characteristics of Pre and GC was analyzed. Results. Elevated expression of miR-421 in plasma can robustly distinguish the normal population from Pre and GC cases, especially in the early stages of gastric cancer cases (all p <0.05). The ROC analyses showed that the area under the ROC curve (AUC), sensitivity, accuracy and Youden index of miR-421 were superior to traditional tumor markers (CEA, CA125, CA153, CA211, and CA50) in GC diagnosis, while its specificity was higher than CEA, CA153 and CA50 (all p <0.05). MiR-421 in plasma had higher AUC value than AFP, CA153, CA211 and CA50 in the diagnosis of Pre (all p<0.05), while specificity, accuracy and Youden index of miR-421 was only lower than CA211. The efficiency of miR-421 in the diagnosis of GC was significantly higher than that of CA211 and CA50, and it was significantly higher than CA153, CA211 and CA50 in the diagnosis of Pre (all p<0.05). In addition, up-regulation of miR-421 occurred initially in precancerous gastric lesions as well as in the early stage of GC. Conclusions. Overexpression of plasma

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Section: Introductionmentioning

confidence: 99%

Peer Review #2 of "Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer (v0.2)"

2019

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“…Given that monocytes of chronic kidney disease (CKD) patients express significantly diminished ACE2 transcripts as compared to healthy control group and miR-421 may not only repress ACE2 expression in primary human cardiac myofibroblasts [24], but is also increased in various pathologic conditions [25][26][27], we aimed to examine whether circulating miR-421 is relevant for leucocytic ACE2. In this study, we investigated the correlation between circulating levels of miR-421 and ACE2 transcripts in circulating leukocytes of CKD patients and healthy individuals (NP).…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-421 Targeting Leucocytic Angiotensin Converting Enzyme 2 Is Elevated in Patients with Chronic Kidney Disease

Trojanowicz

Imdahl²,

Ulrich

et al. 2018

Nephron

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Background: Decreased levels of leucocytic angiotensin converting enzyme 2 (ACE2) relate to atherosclerosis in patients with chronic kidney disease (CKD). Recently, micro RNA 421 (miR-421) was found to target and down-regulate ACE2 in human cardiac myofibroblasts. In this study, we investigated the correlation between serum levels of miR-421 and ACE2 transcripts in circulating leukocytes of healthy individuals (NP), CKD (3–5) and haemodialysis (HD) patients. Furthermore, we tested the possible interaction between miR-421 and 3′-UTR of ACE2 under normal and uremic milieu. Methods: The levels of circulating miR-421, serum Ang1–7 and expression of leucocytic ACE2, ACE, MASR, AT1R and AT2R were investigated in 16 CKD3–5 (76 ± 10 years), 32 HD patients (65 ± 13 years) and 23 NP (51 ± 5 years) by employment of specific primers, TaqMan and competitive enzyme-linked immunosorbent assay assays. Interaction between miR-421 and ACE2–3′-UTR was investigated on THP-1 cells by employment of normal and uremic sera, reporter vectors and miR-421 inhibitor. Effects of uremic toxins indoxyl sulphate, p-cresol and p-cresyl sulphate on ACE2 and miR-421 levels were investigated in THP-1 monocytes. Results: The levels of serum miR-421 were significantly elevated, while Ang1–7 was significantly decreased in CKD3–5 and HD patients as compared with NP. Serum Ang1–7 correlated positively with leucocytic ACE2 (r² = 0.213, p < 0.001). We found a significant and inverse correlation between the levels of circulating miR-421 and the expression of leucocytic ACE2 (r² = 0.223, p < 0.0001). Further significant and positive correlations could be demonstrated between miR-421 and the transcripts of leucocytic AT1R (r² = 0.094, p < 0.05) or eGFR (r² = 0.231, p < 0.0001) or CRP (r² = 0.092, p < 0.01). We found no correlations between miR-421 and ACE or AT2R or MASR expression. Treatment with miR-421 or uremic serum led to noticeable decrease of reporter 3′UTR-ACE2. Anti-miR-421 treatment resulted in the up-regulation of ACE2 protein. All uremic toxins tested were able to significantly elevate miR-421 levels and decrease the monocytic ACE2 transcripts. Conclusions: Uremic patients show an enhanced expression of serum miR-421 as compared to healthy individuals. A strong association of circulating miR-421 with decreased transcripts of ACE2 may contribute to the low expression of the enzyme in leukocytes of CKD patients, further supporting the development of atherosclerotic events.

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“…Increasing evidence revealed that a host of miRNAs are aberrantly expressed in OS patients [5–8]. These deregulated miRNAs might be either proto-oncogenes or anti-oncogenes, depending on their target mRNAs.…”

Section: Introductionmentioning

confidence: 99%

miR-200bc/429 Inhibits Osteosarcoma Cell Proliferation and Invasion by Targeting PMP22

Jiang

Xiao

et al. 2017

Med Sci Monit

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BackgroundMicroRNAs (miRNAs) are small non-coding RNAs which play a crucial role in diverse biological processes and could contribute to cancer development and progression. MiR-200bc/429 have been found to be aberrantly expressed in osteosarcoma (OS). However, the features of miR-200bc/429 in the tumorigenesis and progress of OS remain poorly understood.Material/MethodsThe miR-200bc/429 expression was firstly identified in human OS clinical samples and cell lines by quantitative real-time PCR (qRT-PCR). After transfection with miR-200bc/429 mimics or negative control in U2OS or MG63 cells, cell proliferation was measured by CCK-8 assay. Following that, wound-healing assay and Transwell invasion assay were performed to evaluate cell migration and invasion, respectively. Finally, luciferase reporter assay and Western blot analysis were performed to determine if peripheral myelin protein-22 (PMP22) is a direct target of miR-200bc/429.ResultsResults revealed that miR-200bc/429 were significantly depressed in human OS tissues and cell lines by qRT-PCR. Then, restoration of miR-200bc/429 significantly inhibited cell proliferation (P<0.05) and invasion (P<0.05) in vitro. Luciferase reporter assay and Western blot analysis revealed that miR-200bc/429 could directly target PMP22 3′ untranslated region (UTR) and inhibit its expression in U2OS and MG63 cells.ConclusionsThese findings suggest that miR-200bc/429 inhibit OS cells proliferation and invasion by targeting PMP22, and function as a tumor suppressor and may be a patent molecular marker as well as a potential target for OS therapy.

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miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma

Cited by 53 publications

References 47 publications

Peer Review #2 of "Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer (v0.2)"

Peer Review #2 of "Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer (v0.2)"

Circulating miR-421 Targeting Leucocytic Angiotensin Converting Enzyme 2 Is Elevated in Patients with Chronic Kidney Disease

miR-200bc/429 Inhibits Osteosarcoma Cell Proliferation and Invasion by Targeting PMP22

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