• clinical translation
• gene therapy
• hepatocellular carcinoma
• nanomedicines
• personalized medicine

• Promotion of Science, and Special Education and Researc

• Cancer stem cells
• Drug resistance
• Hepatocellular carcinoma
• Self-renewal
• Targeted therapy

• Humans
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/pathology
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology
• Drug Resistance, Neoplasm/drug effects
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/pharmacology
• Animals
• Molecular Targeted Therapy/methods

• CD markers
• Cancer Stem Cell
• MicroRNAs
• Signaling

• Humans
• MicroRNAs/metabolism
• Neoplasms/metabolism
• Neoplastic Stem Cells/pathology
• Antineoplastic Agents/therapeutic use
• Signal Transduction
• Antigens, Differentiation/metabolism

• dysregulated
• gene targets
• hepatitis B-associated carcinoma (HBV-HCC)
• microRNA (miRNA)
• modulate
• pathways

• Humans
• Carcinoma, Hepatocellular/genetics
• Liver Neoplasms/genetics
• South Africa/epidemiology
• Hepatitis B/complications
• Hepatitis B/genetics
• MicroRNAs/genetics

• HHSN261200800001C NCI NIH HHS
• HHSN261200800001E NCI NIH HHS

• Cancer stem cells
• Hepatocellular carcinoma
• MicroRNAs
• Recurrence.

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths. It is often detected at a stage when there are few therapeutic options. Liver cancer stem cells (LCSCs) are highly tumorigenic and resistant to chemotherapy and radiation therapy. Their presence in HCC is a major reason why HCC is difficult to treat. The development of LCSCs is regulated by a variety of factors. This review summarizes recent advances on the factors that regulate the development of LCSCs. Due to the importance of LCSCs in the development of HCC, a better understanding of how LCSCs are regulated will help to improve the treatments for HCC patients.

• Hepatocellular carcinoma
• Liver cancer stem cells
• Pluripotency transcription factors
• Stem cell signaling
• Genetic regulators
• Epigenetic regulators

Several studies on the prognostic value of microRNA 142 (miR-142) in solid tumors have reported conflicting results. Therefore, the aim of this meta-analysis was to evaluate the relationship between the miR-142 and prognosis in solid tumors. A comprehensive search for relevant studies was conducted until 10 November 2020. Studies that investigated the prognostic significance of the miR-142 in solid tumors were included. The hazard ratio and 95% confidence interval were calculated using a random-effects model. All data analyses were performed using the STATA 12.0 software (Stata Corporation, College Station, TX, U.S.A.). Twenty articles involving 2451 participants were included in the meta-analysis. The results showed that high miR-142 expression was a better predictor of overall survival (OS) (HR = 0.66, 95% CI: 0.47–0.93) and disease-free/progression-free/recurrence-free survival (DFS/PFS/RFS) (HR = 0.71, 95% CI: 0.55–0.91) compared with low miR-142 expression. MiR-142 can be used as an effective prognostic marker for patients with solid tumors. Future large prospective studies are warranted to further confirm the present findings.

• cancer
• meta-analysis
• miR-142
• prognosis

• RAS
• RET
• calcitonin expression and tumor emboli
• disease progression
• immunohistochemistry

• AC133 Antigen/genetics
• AC133 Antigen/metabolism
• Adult
• Aged
• Biomarkers, Tumor/metabolism
• Carcinoma, Medullary/genetics
• Carcinoma, Medullary/metabolism
• Carcinoma, Medullary/pathology
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Mutation
• Prognosis
• Progression-Free Survival
• Proto-Oncogene Proteins c-ret/genetics
• Thyroid Gland/metabolism
• Thyroid Gland/pathology
• Thyroid Neoplasms/genetics
• Thyroid Neoplasms/metabolism
• Thyroid Neoplasms/pathology
• ras Proteins/genetics

• Autophagy
• Cancer
• Chemoresistance
• Hypoxia
• MicroRNA

• AKT signalling pathway
• IL-17F
• prostate cancer
• the PI3K

• apoptosis
• drug target
• hepatic ischemia-reperfusion injury
• inflammation
• miR-142-3p/MARCKS signal

• Animals
• Apoptosis
• Cell Hypoxia
• Disease Models, Animal
• Hep G2 Cells
• Humans
• Inflammation Mediators/metabolism
• JNK Mitogen-Activated Protein Kinases/metabolism
• Liver/metabolism
• Liver/pathology
• Liver Diseases/genetics
• Liver Diseases/metabolism
• Liver Diseases/pathology
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Myristoylated Alanine-Rich C Kinase Substrate/genetics
• Myristoylated Alanine-Rich C Kinase Substrate/metabolism
• NF-kappa B/metabolism
• Phosphatidylinositol 3-Kinase/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Reperfusion Injury/genetics
• Reperfusion Injury/metabolism
• Reperfusion Injury/pathology
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases/metabolism

Cancer stemness, referring to the stem-cell-like phenotype of cancer cells, has been recognised to play important roles in different aspects of hepatocarcinogenesis. A number of well-established cell-surface markers already exist for liver cancer stem cells, with potential new markers of liver cancer stem cells being identified. Both genetic and epigenetic factors that affect various signalling pathways are known to contribute to cancer stemness. In addition, the tumour microenvironment—both physical and cellular—is known to play an important role in regulating cancer stemness, and the potential interaction between cancer stem cells and their microenvironment has provided insight into the regulation of the tumour-initiating ability as well as the cellular plasticity of liver CSCs. Potential specific therapeutic targeting of liver cancer stemness is also discussed. With increased knowledge, effective druggable targets might be identified, with the aim of improving treatment outcome by reducing chemoresistance.

• cancer
• chemoresistance
• chemosensitivity
• circulating
• miRNA
• microRNA
• obesity

• PAK1
• RAC1
• breast cancer
• miR-142-3p

• ER-positive breast cancer
• apoptosis
• cancer stem cell
• estrogen receptor 1
• miR-142-3p

Purpose: Uveal melanoma (UM) is the most frequent metastatic ocular tumor in adults. Therapeutic intervention remains ineffective since none of the novel procedures used to treat this disease increased survival rates. To deal with this limitation, additional studies are required to clarify its pathogenesis. The current study focused on describing how epigenetic modulation by miR-142-3p affects changes in some cellular functions underlying UM pathogenesis.

Methods and results: Microarray analysis identified 374 miRNAs which were differentially expressed between UM cells and uveal melanocytes. miR-142-3p was one of the 10 most downregulated miRNAs. Quantitative RT-PCR analysis confirmed that miR-142-3p expression levels were significantly decreased in both UM cell lines and clinical specimens. The results of the MTS, clone formation, scratch wound, transwell assays, and in vivo biofluorescence imaging showed that miR-142-3p overexpression significantly inhibited cell proliferation, migration, and invasiveness. Nevertheless, miR-142-3p did not affect cell apoptotic activity or sensitivity to doxorubicin. Cell cycle and EdU analysis showed that miR-142-3p overexpression induced G1/G2 cell cycle arrest and reduced DNA synthesis in UM cells. Microarray analysis showed that miR-142-3p mainly regulates the TGFβ signaling pathway, and those in which MAPK and PI3K-Akt are constituents. Functional interactions between miR-142-3p and CDC25C, TGFβR1, GNAQ, WASL, and RAC1 target genes were confirmed based on the results of the luciferase reporter assay and Western blot analysis. CDC25C or RAC1 downregulation is in agreement with cell cycle arrest and DNA synthesis disorder induction, while downregulation of TGFβR1, GNAQ, WASL, or RAC1 accounts for declines in cell migration.

Conclusion: miR-143-3p is a potential therapeutic target to treat UM since overriding its declines in expression that occur in this disease reversed the pathogenesis of this disease. Such insight reveals novel biomarker for decreasing UM vitality and for improved tracking of tumor progression.

• miR-142-3p
• molecular mechanisms
• tumor suppressor
• uveal melanoma

• CD133
• Jak/Stat
• MAPK
• Notch
• PI3K-Akt
• Sonic hedgehog signaling
• TGF-β-SMAD
• WNT
• cancer stem cell
• miRNA

• MALAT1
• Non-small cell lung cancer
• miR-142-3p
• β-catenin

MicroRNA-217 (miR-217) has been demonstrated to participate in the tumorigenesis and progression of various types of cancers. Nevertheless, the role of miR-217 in cervical carcinoma still remains not fully elucidated. This current work sought to investigate the role of miR-217 in the growth, migration, and invasion of cervical carcinoma and detect the role of miR-217 in the chemosensitivity of cervical carcinoma cell to cisplatin.

The levels of miR-217 in 65 pairs of cervical carcinoma tissues and matched normal tissues were detected using quantitative real-time-PCR assay. The roles of miR-217 on the growth, apoptosis, migration, and invasion of cervical cancer SiHa and Ca-Ski cells were analyzed using Cell Counting Kit-8, flow cytometry, wound healing, and Transwell invasion assays, respectively. The target of miR-217 was identified using the online analysis tool TargetScan (http://www.targetscan.org/vert_72/) and was verified by luciferase reporter and immunoblotting assays. The xenograft tumor model was constructed to explore the impact of miR-217 on the growth of cervical carcinoma cell in vivo.

The level of miR-217 was remarkably lower in cervical carcinoma tissues than that in noncancerous tissues. Overregulation of miR-217 markedly suppressed the aggressiveness of cervical cancer cell and induced cell apoptosis through regulating V-Ki-Ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Finally, upregulation of miR-217 enhanced the chemosensitivity of both SiHa and Ca-Ski cervical cancer cells toward cisplatin.

Altogether, upregulation of miR-217 inhibits the aggressiveness phenotypes of cervical carcinoma cell via regulating KRAS gene and increases the sensitivity of cervical cancer cell to cisplatin.

• KRAS
• cervical cancer
• cisplatin
• miR-217

• cancer stem cells
• hepatocellular carcinoma
• inhibitors
• target
• therapy

• Research Grants Council, University Grants Committee
• National Natural Science Foundation of China
• CUHK Direct Grant

• cancer therapy
• microRNA-142
• osteosarcoma

• Liver regeneration
• MicroRNA
• Microvesicles
• Partial hepatectomy
• Purinergic signaling
• Vascular inflammation

• BRCA
• Breast cancer
• cancer stem cells
• mammospheres
• miR-142-3p
• radiation

• EMT
• MicroRNA (miRNA)
• cancer stem cell (CSC)
• chemo-resistance
• liver cancer

• apoptosis
• microRNA-142
• osteosarcoma
• proliferation

• Animals
• Humans
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• MicroRNAs/metabolism
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• RNA, Long Noncoding/metabolism
• RNA, Neoplasm/metabolism

• AC133 Antigen/antagonists & inhibitors
• AC133 Antigen/genetics
• AC133 Antigen/metabolism
• Apoptosis
• Cell Cycle
• Cell Proliferation
• Cells, Cultured
• Fetal Blood/cytology
• Fetal Blood/metabolism
• Fetal Blood/radiation effects
• Gene Expression Regulation, Neoplastic/radiation effects
• Humans
• Leukocytes, Mononuclear/cytology
• Leukocytes, Mononuclear/metabolism
• Leukocytes, Mononuclear/radiation effects
• MicroRNAs/genetics
• Mitogen-Activated Protein Kinase 1/genetics
• Mitogen-Activated Protein Kinase 1/metabolism
• Mitogen-Activated Protein Kinase 3/genetics
• Mitogen-Activated Protein Kinase 3/metabolism
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Radiation Tolerance

• cyclin T2
• gastric cancer
• microRNA-142-3p
• tumor suppressor

• HDAC5
• differentiation
• lung cancer stem cells
• miR-2861

Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain “purified” CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma.

• cancer stem cell markers
• cancer stem cells
• cervical cancer
• cervical cancer stem cells
• chemo/radio-resistance

• Aerobic glycolysis
• Hepatocellular carcinoma
• LDHA
• Proliferation
• miR-142-3p

• Aerobiosis
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Proliferation
• Gene Expression Regulation, Neoplastic/genetics
• Glucose/metabolism
• Glycolysis
• Humans
• Lactate Dehydrogenases/metabolism
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• MicroRNAs/metabolism
• Oxygen/metabolism
• Protein Binding
• Tumor Cells, Cultured

Poor prognosis and high recurrence remain leading causes of primary liver cancerassociated mortality. The spread of circulating tumor cells (CTCs) in the blood plays a major role in the initiation of metastasis and tumor recurrence after surgery. Nevertheless, only a subset of CTCs can survive, migrate to distant sites and establish secondary tumors. Consistent with cancer stem cell (CSC) hypothesis, stem-like CTCs might represent a potential source for cancer relapse and distant metastasis. Thus, identification of stem-like metastasis-initiating CTC-subset may provide useful clinically prognostic information. This review will emphasize the most relevant findings of CTCs in the context of stem-like biology associated to liver carcinogenesis. In this view, the emerging field of stem-like CTCs may deliver substantial contribution in liver cancer field in order to move to personalized approaches for diagnosis, prognosis and therapy.

• cancer stem cells
• circulating tumor cells
• primary liver cancer

• CD133
• Cancer stem cells (CSCs)
• Renal cell carcinoma (RCC)
• Tissue microarray (TMA)

• CD133(+) cells
• HCV
• Hepatocellular carcinoma

• AC133 Antigen/metabolism
• Adult
• Aged
• Aged, 80 and over
• Biomarkers
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/pathology
• Case-Control Studies
• Cluster Analysis
• Female
• Gene Expression Profiling
• Hepatitis C/complications
• Humans
• Immunomagnetic Separation
• Immunophenotyping
• Liver Function Tests
• Liver Neoplasms/etiology
• Liver Neoplasms/pathology
• Male
• Middle Aged
• Neoplastic Cells, Circulating/metabolism
• Neoplastic Cells, Circulating/pathology
• Neoplastic Stem Cells/metabolism
• Transcriptome

• HMGB1
• lncRNA-MALAT1
• miR-129–5p
• miR-142–3p
• osteosarcoma

• CD133
• cancer stem cell
• meta-analysis
• tumor genesis
• tumor recurrence

• Cancer stem cells
• Hepatocellular carcinoma
• Molecular alterations
• Next-generation sequencing

Myocardial ischemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as cardiac fibrosis, which is characterized as the transdifferentiation of fibroblasts to myofibroblasts and collagen deposition. MicroRNAs (miRNAs or miRs) have been demonstrated to be involved in myocardial I/R injury. However, the underlying molecular mechanism remains largely unclear. In the present study, mouse cardiomyocyte M6200 cells were treated with hypoxia/reoxygenation (H/R). Our data indicated that H/R treatment led to cell apoptosis, the increased expression of fibrosis-related proteins, namely collagen I, II, III, and fibronectin, as well as the downregulation of miR-142-3p in M6200 cells. Overexpression of miR-142-3p suppressed the H/R-induced apoptosis and fibrosis of M6200 cells. Bioinformatics analysis and a Dual-Luciferase reporter assay further identified high mobility group box 1 (HMGB1) as a direct target gene of miR-142-3p, and miR-142-3p negatively regulated the protein level of HMGB1 in M6200 cells. Furthermore, knockdown of HMGB1 enhanced cell proliferation whereas it inhibited the apoptosis and fibrosis of M6200 cells. In addition, TGF-β1/Smad3 signaling was suggested to be involved in the miR-142-3p/HMGB1-mediated apoptosis and fibrosis of M6200 cells treated with H/R. Taken together, the findings of the present study demonstrate that miR-142-3p inhibits H/R-induced apoptosis and fibrosis of cardiomyocytes, partly at least, by the direct inhibition of HMGB1 expression. Therefore, these findings have increased our understanding of the pathogenesis of H/R-induced myocardial injury.

CD133 is one of the most commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CD133 in gastric cancer remains controversial. To clarify a precise determinant of the clinical significance of CD133, we conducted a systematic review and meta-analysis to elucidate the correlation of CD133 overexpression with prognosis and clinicopathological features of GC patients.

A search in the Cochrane Library, Pubmed, Medline, Web of Knowledge and Chinese CNKI, CBM (up to Jun 30, 2015) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.2.0 software was used for meta-analysis.

A total of 603 gastric cancer patients from 8 studies were included. The results of the meta-analyses showed that, there were significant differences of CD133 expression in the following comparisons: gastric cancer tissues vs. normal esophageal tissue (OR = 3.49, 95% CI [2.48, 490], P < 0.00001), lymph node metastasis vs. non-lymph node metastasis (OR = 2.75, 95% CI [1.99, 3.81], P < 0.00001), distant metastasis vs. non-distant metastasis (OR = 2.38, 95%CI [1.47, 3.85], P < 0.0004), clinical stages III~IV vs. clinical stages I~II (OR = 2.83, 95% CI [2.13, 3.76], P < 0.00001), as well as the accumulative 5-year overall survival rates of CD133-positive vs. CD133-negative patients (OR = 0.23, 95% CI [0.16, 0.33], P < 0.00001).

Overexpression of CD133 is associated with lymph node metastasis, distant metastasis, poor TNM stage. Additionally, CD133-positive gastric cancer patients had worse prognosis. Our results indicate that CD133 may be involved in the carcinogenesis of gastric cancer. Evaluation of cytoplasmic CD133 overexpression in gastric cancer tissue sections may be useful in the future as a novel prognostic factor. Nevertheless, due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.

• CD133
• CSC
• IHC
• gastric cancer

Cancer represents a complex disease originated from alterations in several genes leading to disturbances in important signaling pathways in tumor biology, favoring heterogeneity that promotes adaptability and pharmacological resistance of tumor cells. Metabolic reprogramming has emerged as an important hallmark of cancer characterized by the presence of aerobic glycolysis, increased glutaminolysis and fatty acid biosynthesis, as well as an altered mitochondrial energy production. The metabolic switches that support energetic requirements of cancer cells are closely related to either activation of oncogenes or down-modulation of tumor-suppressor genes, finally leading to dysregulation of cell proliferation, metastasis and drug resistance signals. Non-coding RNAs (ncRNAs) have emerged as one important kind of molecules that can regulate altered genes contributing, to the establishment of metabolic reprogramming. Moreover, diverse metabolic signals can regulate ncRNA expression and activity at genetic, transcriptional, or epigenetic levels. The regulatory landscape of ncRNAs may provide a new approach for understanding and treatment of different types of malignancies. In this review we discuss the regulatory role exerted by ncRNAs on metabolic enzymes and pathways involved in glucose, lipid, and amino acid metabolism. We also review how metabolic stress conditions and tumoral microenvironment influence ncRNA expression and activity. Furthermore, we comment on the therapeutic potential of metabolism-related ncRNAs in cancer.

• cancer metabolism
• metabolic reprogramming
• miRNAs
• ncRNA regulation

• Angiogenesis
• Cancer stem cells
• Hepatocellular carcinoma
• Tumor microenvironment

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide malignancy and the third leading cause of cancer death in patients. Several studies demonstrated that hepatic cancer stem cells (HCSCs), also called tumor-initiating cells, are involved in regulation of HCC initiation, tumor progression, metastasis development, and drug resistance. Despite the extensive research, the underlying mechanisms by which HCSCs are regulated remain still unclear. MicroRNAs (miRNAs) are able to regulate a lot of biological processes such as self-renewal and pluripotency of HCSCs, representing a new promising strategy for treatment of HCC chemotherapy-resistant tumors. In this review, we synthesize the latest findings on therapeutic regulation of HCSCs by miRNAs, in order to highlight the perspective of novel miRNA-based anticancer therapies for HCC treatment.

Alpha fetoprotein (AFP) is a clinical biomarker of hepatocellular carcinoma (HCC). Here, we found that miR-1236 is down-regulated, whereas AFP is highly expressed in HCC tissues and cells. We demonstrated that miR-1236 directly targets the 3′UTR of AFP and down-regulates its expression. Also, miR-1236 inhibited and AFP stimulated proliferation, migration, invasion and vasculogenic mimicry (VM) of HCC. In agreement, AFP over-expression counteracted the inhibitory effect of miR-1236. We demonstrated that AFP promoted the ubiquitination of PTEN, thus decreasing PTEN levels, while miR-1236 inhibited the PI3K/Akt pathway.

• AFP
• PTEN
• hepatocellular cancer
• microRNA
• microRNA-1236

Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell-surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133.