Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumor-specific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.

/pdf/the-emerging-role-of-micrornas-and-long-noncoding-rnas-in-24pvjz8ga4.pdf

The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

The role of miRNAs in colorectal cancer progression and chemoradiotherapy.

Cyclic nucleotide phosphodiesterases (PDE) break down cyclic nucleotides such as cAMP and cGMP, reducing the signaling of these important intracellular second messengers. Several unique families of phosphodiesterases exist, and certain families are clinically important modulators of vasodilation. In the current work, we have summarized the body of literature that describes an emerging role for the PDE4 subfamily of phosphodiesterases in malignancy. We have systematically investigated PDE4A, PDE4B, PDE4C, and PDE4D isoforms and found evidence associating them with several cancer types including hematologic malignancies and lung cancers, among others. In this review, we compare the evidence examining the functional role of each PDE4 subtype across malignancies, looking for common signaling themes, signaling pathways, and establishing the case for PDE4 subtypes as a potential therapeutic target for cancer treatment.

PDE4 subtypes in cancer.

This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma (ESCC), which if diagnosed at advanced stages has <30% five-year survival rate. Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues, we identified 35,577 differentially methylated CpG sites (DMCs) and characterized their distribution patterns. Integrating whole-genome DNA and RNA-sequencing data of the same samples, we found multiple dysregulated transcription factors and ESCC-specific genomic correlates of identified DMCs. Using featured DMCs, we developed a 12-marker diagnostic panel with high accuracy in our dataset and the TCGA ESCC dataset, and a 4-marker prognostic panel distinguishing high-risk patients. In-vitro experiments validated the functions of 4 marker host genes. Together these results provide additional evidence for the important roles of aberrant DNA methylations in ESCC development and progression. Our DMC-based diagnostic and prognostic panels have potential values for clinical care of ESCC, laying foundations for developing targeted methylation assays for future non-invasive cancer detection methods. 

/pdf/multi-omic-characterization-of-genome-wide-abnormal-dna-1ypvq1zw.pdf

Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma

Background MicroRNAs (miRNAs) is a class of functional regulator of tumorigenesis of human cancer including hepatocellular carcinoma (HCC). However, the potential clinical significance of serum exosomal miR-320d in HCC has not been elucidated. Methods Real-time reverse transcription PCR was used to detect the expression pattern of serum exosomal miR-320d in patients with HCC, and the correlation between the deregulation of serum exosomal miR-320d and the clinical outcome of HCC was explored. The biological function of exosomal miR-320d in HCC was also investigated. Results Our results showed that the expression levels of exosomal miR-320d were remarkably reduced in the serum samples of HCC patients and the culture medium of HCC cell lines compared with their respective controls. Serum exosomal miR-320d could differentiate the HCC patients from healthy controls with high accuracy. In addition, its level was remarkably increased in the HCC patients who had received surgical treatment. Moreover, reduced serum exosomal miR-320d was associated with advanced tumor stage, positive lymph node metastasis, and poorly differentiated tumors. HCC patients with lower serum exosomal miR-320d had shorter overall and disease-free survival. Low serum exosomal miR-320d was identified to be an independent unfavorable prognostic factor for HCC. Finally, overexpression of miR-320d inhibited the proliferation and invasion of HCC cells, and BMI1 was demonstrated to be a direct target of miR-320d. Conclusion Taken together, serum exosomal miR-320d could be a potential non-invasive biomarker for the diagnosis and prognosis of HCC.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.23239

Downregulation of serum exosomal miR-320d predicts poor prognosis in hepatocellular carcinoma

Homoharringtonine Synergizes Strongly with Venetoclax Against the Early T-Cell Progenitor Acute Lymphoblastic Leukemia：from Bench to Bed

Targeting miR-126 in Ph+ acute lymphoblastic leukemia

Homoharringtonine Exhibits Anti-Tumor Effect in T-Cell Acute Lymphoblastic Leukemia By Targeting Notch1/Myc Pathway

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. microRNA has been reported playing an important role in a variety of cancers including colorectal cancer. miR-203a-3p has been found up-regulated in CRC tissues compare with the adjacent normal tissues. But, how miR-203a-3p regulates CRC development remains to be elucidated. In this study, gain and loss-of-function assays showed that miR-203a-3p promotes colorectal cancer cell proliferation, colony formation and migration and invasion by targeting PDE4D. And miR-203a-3p/β-catenin/Cyclin D1/c-Myc signaling pathway is involved in the CRC. In summary, this study highlights an onco-miRNA role for miR-203a-3p by regulating PDE4D in CRC and suggests that miR-203a-3p may be a novel molecular therapeutic target for CRC.

miR-203a-3p promotes colorectal cancer proliferation and migration by targeting PDE4D.

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Homoharringtonine Synergizes Strongly with Venetoclax Against the Early T-Cell Progenitor Acute Lymphoblastic Leukemia：from Bench to Bed

Targeting miR-126 in Ph+ acute lymphoblastic leukemia

Homoharringtonine Exhibits Anti-Tumor Effect in T-Cell Acute Lymphoblastic Leukemia By Targeting Notch1/Myc Pathway

miR-203a-3p promotes colorectal cancer proliferation and migration by targeting PDE4D.