miR-106b-5p promotes stem cell-like properties of hepatocellular carcinoma cells by targeting PTEN via PI3K/Akt pathway

Shi, Dongmin; Bian, Xinyu; Qin, Chengdong; Wu, Wei‐Zhong

doi:10.2147/ott.s152611

Cited by 53 publications

(39 citation statements)

References 36 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among these six miRNAs, miR-106b-5p has been reported to promote stemlike properties of HCC cells via targeting PTEN, consistent with our present study (Shi et al 2018). However, the expression level of miR-125b-5p increased in the serum of HBV-positive HCC patients compared with matched controls, which is contradictory to our findings (Giray et al 2014).…”

Section: Discussionsupporting

confidence: 92%

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Zhu

Huang

et al. 2018

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

show abstract

Section: Discussionsupporting

confidence: 92%

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Zhu

Huang

et al. 2018

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…Furthermore, Pten deficiency promotes tumorigenicity, and approximately 50% of human cases of HCC lose PTEN expression . In fact, several micro‐RNAs can downregulate PTEN expression during progression of human HCC . Here, we demonstrated that hypercholesterolemia promotes tumor growth by accelerating angiogenesis in Pten Δhep mice.…”

Section: Introductionmentioning

confidence: 71%

“…19 In fact, several micro-RNAs can downregulate PTEN expression during progression of human HCC. 20,21 Here, we demonstrated that hypercholesterolemia promotes tumor growth by accelerating angiogenesis in Pten Δhep mice. Ezetimibe lowered cholesterol levels and inhibited angiogenesis, resulting in suppression of liver tumors in Pten Δhep mice on a high-fat (HF) diet.…”

mentioning

confidence: 88%

Ezetimibe suppresses development of liver tumors by inhibiting angiogenesis in mice fed a high‐fat diet

et al. 2019

View full text Add to dashboard Cite

Nonalcoholic steatohepatitis (NASH) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC). However, effective therapeutic strategies for preventing and treating NASH‐mediated liver cirrhosis and HCC are lacking. Cholesterol is closely associated with vascular endothelial growth factor (VEGF), a key factor that promotes HCC. Recent reports have demonstrated that statins could prevent HCC development. In contrast, we have little information on ezetimibe, an inhibitor of cholesterol absorption, in regards to the prevention of NASH‐related liver cirrhosis and HCC. In the present study, a steatohepatitis‐related HCC model, hepatocyte‐specific phosphatase and tensin homolog (Pten)‐deficient (Pten Δhep) mice were fed a high‐fat (HF) diet with/without ezetimibe. In the standard‐diet group, ezetimibe did not reduce the development of liver tumors in Pten Δhep mice, in which the increase of serum cholesterol levels was mild. Feeding of a HF diet increased serum cholesterol levels markedly and subsequently increased serum levels of VEGF, a crucial component of angiogenesis. The HF diet increased the number of VEGF‐positive cells and vascular endothelial cells in the tumors of Pten Δhep mice. Kupffer cells, macrophages in the liver, increased VEGF expression in response to fat overload. Ezetimibe treatment lowered cholesterol levels and these angiogenetic processes. As a result, ezetimibe also suppressed inflammation, liver fibrosis and tumor growth in Pten Δhep mice on the HF diet. Tumor cells were highly proliferative with HF‐diet feeding, which was inhibited by ezetimibe. In conclusion, ezetimibe suppressed development of liver tumors by inhibiting angiogenesis in Pten Δhep mice with hypercholesterolemia.

show abstract

“…PTEN deletion results in the proliferation of a CD133+ population [71,98] . PI3K signaling promotes stem-like properties of HCC cells and it is implicated in HCC chemo-and radio-resistance as well as in epithelial-to-mesenchymal transition (EMT) and metastasis [99][100][101][102][103][104] . Notably, the co-activation of AKT and neuroblastoma rat sarcoma viral oncogene homolog (N-RAS) oncogenes leads to development of cHCC-CCA-like liver tumors, through the expansion of HPCs or malignant conversion of hepatocyte into progenitor-like cells [42] .…”

Section: Phosphatidyl Inositol 3-kinase/akt Signalingmentioning

confidence: 99%

Stemness features in liver cancer

Correnti¹,

Booijink²,

Maira³

et al. 2018

View full text Add to dashboard Cite

Heterogeneity is a cardinal hallmark of cancer, including primary liver cancer (PLC), and occurs at different layers including putative cell-of-origin. Current evidence suggests that within cellular subpopulations in PLC there are stem-like cells, the cancer stem cells (CSCs). The CSC concept has been recently proposed as an explanation of such intra-tumor heterogeneity. According to this model, CSCs are responsible for tumor initiation, recurrence, metastasis as well as drug-resistance. However, although the CSC hypothesis is intriguing and supported by a large number of experimental studies, there are still open questions regarding the origin of putative CSCs. Since chemoresistance and recurrence represent major issues in PLC treatment, the development of new therapeutic strategies is needed, for which a good understanding of tumor behavior and in particular of CSCs biology is an imperative prerequisite. In this review we summarize the regulatory pathways that support CSC features in PLC. Moreover, we highlight the key features of hepatic CSC, in terms of enhanced drug-resistance, increased metastatic potential and metabolic rearrangement. Knowledge of the molecular mechanisms underlying CSC biology may provide novel options for PLC combination therapies.Primary liver cancer (PLC) is one of the most common cancers worldwide and the second leading cause of cancer-related mortality [1,2] . The major forms of PLC comprise hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) [1,3-5] . HCC accounts for approximately 90% of all PLCs [1,3] , while CCA is the second most common form and accounts for about 5% of all PLCs [3][4][5] . HCC causes over 600,000 deaths worldwide annually, and its incidence and mortality are increasing at a fast rate [6-10] . On the other hand, CCA is characterized by a very poor prognosis, with a 5-years survival lower than 20%, and its incidence and worldwide mortality are also increasing [5,[11][12][13] . The high mortality rate of CCA may depend on its nonspecific or silent clinical features and the lack of specific markers that make it difficult to diagnose [14][15][16] .Many studies carried out in these last years have attempted to define which type of epithelial cell [hepatocytes, cholangiocytes, hepatic progenitor cells (HPCs) or all three] should be considered as the PLC cell of origin [17] . For a long time, HCC and CCA have been commonly accepted to derive from hepatocytes and cholangiocytes, respectively. Since mature hepatocytes and cholangiocytes have an enormous selfrenewal capacity and longevity, they meet the requirements to be targets for oncogenesis [17][18][19][20][21][22][23] . Detailed analyses of a wide range of PLC tumor types have reported that a rare form of combined HCC-CCA (cHCC-CCA) has intermediate characteristics between HCC and intrahepatic CCA (iCCA), suggesting that they could share the same stem/progenitor cell origin [18][19][20][21][22][23][24] . In this regard, since most PLCs arise on the background of chronic liver disease in the presence of an ex...

show abstract

miR-106b-5p promotes stem cell-like properties of hepatocellular carcinoma cells by targeting PTEN via PI3K/Akt pathway

Cited by 53 publications

References 36 publications

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Ezetimibe suppresses development of liver tumors by inhibiting angiogenesis in mice fed a high‐fat diet

Stemness features in liver cancer

Contact Info

Product

Resources

About