Value of Serum miRNA-96-5p and miRNA-99a-5p as Diagnostic Biomarkers for Hepatocellular Carcinoma

Gharib, Amal F.; Eed, Emad M.; Khalifa, Amany Salah; Raafat, Nermin; Shehab-Eldeen, Somaia; Alwakeel, Hany R.; Darwiesh, Ehab; Essa, Abdallah

doi:10.2147/ijgm.s354842

Cited by 15 publications

(11 citation statements)

References 42 publications

(45 reference statements)

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“…Most significant decreases were observed in EV-associated miR-451a, miR-374a-5p, miR-96-5p, and miR-16-5p. Of the top ten dysregulated miRNAs, miR-25-3p, miR-96-5p, and miR-30a-5p have been reported as biomarkers for discriminating hepatocellular carcinoma patients (11,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). Amongst them, miR-25-3p has been shown to promote hepatocellular carcinoma cell growth, migration, and invasion (54).…”

Section: Discussionmentioning

confidence: 99%

Profiling plasma extracellular vesicle-derived microRNAs for noninvasive diagnosis of alpha-1 antitrypsin deficiency associated liver disease

Oshins,

Huo,

Poole

et al. 2023

Preprint

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Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease characterized by reduced circulating levels of alpha-1 antitrypsin (AAT) due to the retention of misfolded AAT in the hepatocytes. The toxic AAT aggregates in hepatocytes cause liver fibrosis, cirrhosis, and hepatocellular carcinoma. Most patients remain asymptomatic until the final stage in which liver transplantation becomes the only treatment. Timely diagnosis of AATD liver disease plays a critical role in intervention and finding curative solutions. Assessing the prevalence and severity of AATD liver disease remains challenging due to limitations in current methods. Liver biopsy, the gold standard for evaluating the hepatic AAT accumulation, the initiating stage for AATD liver disease, is hindered by invasiveness and sampling errors. To address these limitations, we conducted a study using unique and precious clinical samples. We analyzed plasma extracellular vesicle (EV) derived miRNAs and liver transcriptomes from AATD individuals to develop a sensitive and noninvasive diagnostic approach for AATD liver disease. In the testing stage of our study, we enrolled 17 AATD individuals with different stages of liver disease, as determined by liver biopsy, and 20 controls. We identified differential expression of 178 miRNAs within the AATD group compared to controls by miRNA sequencing. Among those miRNAs, we selected miR-223-3p, miR-23a-3p, miR-15b-5p, let-7a-5p, let-7f-5p, and miR-374a-5p for further validation in an independent cohort of 45 AATD individuals. Using a logistic model that combined three miRNAs, we achieved an AUC of 0.737 for detecting AATD liver disease. Adding a fourth miRNA into this model increased the AUC to 0.751. The changes in EV miRNAs are correlated to dysregulated expression of liver mRNAs in AATD individuals with different stages of liver disease. We propose that plasma-circulating EV exhibit distinct miRNAs in AATD individuals and could serve as clinically significant biomarkers for the early detection of AATD liver disease.

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Section: Discussionmentioning

confidence: 99%

Profiling plasma extracellular vesicle-derived microRNAs for noninvasive diagnosis of alpha-1 antitrypsin deficiency associated liver disease

Oshins,

Huo,

Poole

et al. 2023

Preprint

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“…Therefore, miR-96-5p continually up-regulated in HCC inhibits apoptosis by targeting CASP9. Accordingly, miR-96-5p may be a possible therapeutic target for HCC [ 81 ]. Combined miR-96-5 p with AFP induced sensitivity of HCC detection.…”

Section: Function Of Oncogenic Mirs In Hepatocellular Carcinomamentioning

confidence: 99%

“…In addition, its serum levels were linked to tumor growth and migration. These results suggested that serum miR-96-5p can be used as a non-invasive biomarker for HCC detection [ 81 ].…”

Section: Function Of Oncogenic Mirs In Hepatocellular Carcinomamentioning

confidence: 99%

The role of microRNAs in hepatocellular carcinoma: Therapeutic targeting of tumor suppressor and oncogenic genes

Farsi,

Naghipour,

Shahabi

et al. 2023

ceh

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Hepatocellular carcinoma (HCC) is a severe malignant liver cancer with a poor prognosis and a high mortality rate. This carcinoma is a multistage process that begins with chronic hepatitis and progresses to cirrhosis, dysplastic nodules, and eventually HCC. However, the exact molecular etiology remains unclear. MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of numerous genes. These molecules have become significant participants in several functions, including cell proliferation, differentiation, development, and tumorrelated properties. They have a pivotal role in carcinogenesis as oncogenes or tumor suppressor genes. Furthermore, some investigations have shown that particular miRs might be used as predictive or diagnostic markers and therapeutic targets in HCC therapy. This review study summarizes the current level of knowledge on the role of miRs in the initiation and progression of HCC.

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“…Circulating miRNAs (miRs) have been increasingly recognized as potential biomarkers in cancer [ 25 , 26 ]. Serum levels of miR-141 and miR-200a were decreased in hepatocellular carcinoma and could predict cancer metastasis [ 27 ].…”

Section: Mir-200 Family As a Diagnostic And Prognostic Markermentioning

confidence: 99%

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

Shim

Jeoung

2022

IJMS

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MicroRNAs (miRNAs) are small non-coding RNAs (18–24 nucleotides) that play significant roles in cell proliferation, development, invasion, cancer development, cancer progression, and anti-cancer drug resistance. miRNAs target multiple genes and play diverse roles. miRNAs can bind to the 3′UTR of target genes and inhibit translation or promote the degradation of target genes. miR-200 family miRNAs mostly act as tumor suppressors and are commonly decreased in cancer. The miR-200 family has been reported as a valuable diagnostic and prognostic marker. This review discusses the clinical value of the miR-200 family, focusing on the role of the miR-200 family in the development of cancer and anti-cancer drug resistance. This review also provides an overview of the factors that regulate the expression of the miR-200 family, targets of miR-200 family miRNAs, and the mechanism of anti-cancer drug resistance regulated by the miR-200 family.

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Value of Serum miRNA-96-5p and miRNA-99a-5p as Diagnostic Biomarkers for Hepatocellular Carcinoma

Cited by 15 publications

References 42 publications

Profiling plasma extracellular vesicle-derived microRNAs for noninvasive diagnosis of alpha-1 antitrypsin deficiency associated liver disease

Profiling plasma extracellular vesicle-derived microRNAs for noninvasive diagnosis of alpha-1 antitrypsin deficiency associated liver disease

The role of microRNAs in hepatocellular carcinoma: Therapeutic targeting of tumor suppressor and oncogenic genes

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

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