Hepatocellular carcinoma (HCC) is one of the most common cancers, leading to the second cancer-related death in the global. Although the treatment of HCC has greatly improved over the past few decades, the survival rate of patients is still quite low. Thus, it is urgent to explore new therapies, especially seek for more accurate biomarkers for early diagnosis, treatment and prognosis in HCC. MicroRNAs (miRNAs), small noncoding RNAs, are pivotal participants and regulators in the development and progression of HCC. Great progress has been made in the studies of miRNAs in HCC. The key regulatory mechanisms of miRNAs include proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in HCC. And exosomal miRNAs also play important roles in proliferation, invasion, metastasis, and drug resistance in HCC by regulating gene expression in the target cells. In addition, some miRNAs, including exosomal miRNAs, can be as potential diagnostic and prediction markers in HCC. This review summarizes the latest researches development of miRNAs in HCC in recent years.

/pdf/the-role-of-micrornas-in-hepatocellular-carcinoma-2bmkiq30x2.pdf

The Role of MicroRNAs in Hepatocellular Carcinoma.

Emerging evidence shows that Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a pivotal role in cell proliferation, migration, and invasion in tumors. However, the biological role and underlying mechanism of MALAT1 in liver fibrosis remains undefined. In this study, up-regulation of MALAT1 was observed in fibrotic liver tissues and in activated hepatic stellate cells (HSCs). In addition, depletion of MALAT1 inhibited the activation of HSCs in vitro and attenuated collagen deposits in vivo. Our results demonstrated that MALAT1 expression is negatively correlated with microRNA-101b (miR-101b) expression. Furthermore, there was a negative feedback loop between the levels of MALAT1 and miR-101b. Luciferase reporter assay indicated that MALAT1 and RAS-related C3 botulinum substrate 1 (Rac1) are targets of miR-101b. We uncovered that MALAT1 regulates Rac1 expression through miR-101b as a competing endogenous RNA (ceRNA), thereby influencing the proliferation, cell cycle and activation of primary HSCs. Collectively, The ceRNA regulatory network may prompt a better understanding of liver fibrogenesis and contribute to a novel therapeutic strategy for liver fibrosis.

https://www.tandfonline.com/doi/pdf/10.1080/15384101.2015.1120917

MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis.

Liver cancer is the fourth leading cause of cancer deaths globally, of which hepatocellular carcinoma (HCC) is the major subtype. Viral hepatitis B and C infections, alcohol abuse, and metabolic disorders are multiple risk factors for liver cirrhosis and HCC development. Although great therapeutic advances have been made in recent decades, the prognosis for HCC patients remains poor due to late diagnosis, chemotherapy failure, and frequent recurrence. MicroRNAs (miRNAs) are endogenous, non-coding RNAs that regulate various molecular biological phenomena by suppressing the translation of target messenger RNAs (mRNAs). miRNAs, which often become dysregulated in malignancy, control cell proliferation, migration, invasion, and development in HCC by promoting or suppressing tumors. Exploring the detailed mechanisms underlying miRNA-mediated HCC development and progression can likely improve the outcomes of patients with HCC. This review summarizes the molecular and functional roles of miRNAs in the pathogenesis of HCC. Further, it elucidates the utility of miRNAs as novel biomarkers and therapeutic targets.

https://www.mdpi.com/1422-0067/21/21/8362/pdf

Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma-A Review.

Hepatocellular carcinoma (HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called "liquid biopsy" is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma.

Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids.

Hepatocellular carcinoma (HCC) is the seventh most frequent cancer and the fourth leading cause of cancer mortality worldwide. Despite substantial advances in therapeutic strategies, the prognosis of late-stage HCC remains dismal because of the high recurrence rate. A better understanding of the etiology of HCC is therefore necessary to improve outcomes. MicroRNAs (miRNAs) are small, endogenous, noncoding, single-stranded RNAs that modulate the expression of their target genes at the posttranscriptional and translational levels. Aberrant expression of miRNAs has frequently been detected in cancer-associated genomic regions or fragile sites in various human cancers and has been observed in both HCC cells and tissues. The precise patterns of aberrant miRNA expression differ depending on disease etiology, including various causes of hepatocarcinogenesis, such as viral hepatitis, alcoholic liver disease, or nonalcoholic steatohepatitis. However, little is known about the underlying mechanisms and the association of miRNAs with the pathogenesis of HCC of various etiologies. In the present review, we summarize the key mechanisms of miRNAs in the pathogenesis of HCC and emphasize their potential utility as valuable diagnostic and prognostic biomarkers, as well as innovative therapeutic targets, in HCC diagnosis and treatment.

https://www.mdpi.com/2072-6694/13/3/514/pdf

MicroRNAs in the Pathogenesis of Hepatocellular Carcinoma: A Review.

MicroRNAs (miRNAs) represent a class of evolutionarily conserved, non-coding small RNAs (18–25 nt) that have emerged as master regulators of several biological processes. Recently, circulating miRNAs have also been reported to be promising biomarkers for various pathological conditions. In the present study, we report the comparative expression profiling of microRNA-101 (miR-101) in serum and tissue samples from chronic hepatitis B (CHB), HBV-associated liver cirrhosis (HBV-LC), and HBV-associated hepatocellular carcinoma (HBV-HCC) patients and healthy controls. The serum miR-101 levels were found to be significantly downregulated in the HBV-HCC patients compared with the HBV-LC patients (P < 0.001), CHB patients (P < 0.001) and healthy controls but were upregulated in the HBV-LC patients compared with the CHB patients (P < 0.001) and healthy controls (P < 0.001). Consistent with the serum data, the expression of miR-101 was also upregulated and downregulated in the HBV-LC and HBV-HCC tissue samples, respectively. A receiver operating characteristic (ROC) analysis of serum miR-101 yielded an area under the ROC curve (AUC) of 0.976 with 95.5% sensitivity and 90.2% specificity when differentiating between HBV-HCC and HBV-LC. Our results suggest that the serum miR-101 level can serve as a potential non-invasive biomarker to differentiate HBV-HCC from HBV-LC.

https://www.tandfonline.com/doi/pdf/10.4161/cbt.29688

Expression profiling of serum microRNA-101 in HBV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

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Expression profiling of serum microRNA-101 in HBV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma