Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
MicroRNA‐24‐3p (miR‐24‐3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer‐associated fibroblasts (CAFs) can secret exosomes to transfer ...miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF‐derived exosomal miR‐24‐3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF‐derived exosomal miR‐24‐3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR‐24‐3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR‐24‐3p was verified using ChIP and dual‐luciferase reporter gene assays. Exosomes were isolated from miR‐24‐3p inhibitor–treated CAFs (CAFs‐exo/miR‐24‐3p inhibitor), which were used in combination with gain‐of‐function and loss‐of‐function experiments and MTX treatment. CCK‐8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR‐24‐3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR‐24‐3p and could up‐regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down‐regulated miR‐24‐3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR‐24‐3p was transferred into CC cells via CAF‐derived exosomes. CAF‐derived exosomal miR‐24‐3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF‐derived exosomal miR‐24‐3p accelerated resistance of CC cells to MTX by down‐regulating CDX2/HEPH axis.
Proteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.
Here, we analyzed the proteomes ...and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue.
We identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1
and PARP4
) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance.
Our proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis.
ClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .
There is increasing evidence that liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) initiation and progression. MicroRNA (miRNA) plays a significant functional role by ...directly regulating respective targets in LCSCs-triggered HCC, however, little is known about the function of the miRNA-302 family in LCSCs.
MiRNAs microarray was used to detect the miRNAs involved in LCSCs maintenance and differentiation. Biological roles and the molecular mechanism of miRNA-302a/d and its target gene E2F7 were detected in HCC in vitro. The expression and correlation of miRNA-302a/d and E2F7 in HCC patients was evaluated by quantitative PCR and Kaplan-Meier survival analysis.
We found that the miRNA-302 family was downregulated during the spheroid formation of HCC cells and patients with lower miRNA-302a/d expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, E2F7 was confirmed to be directly targeted and inhibited by miRNA-302a/d. Furthermore, concomitant low expression of miRNA-302a/d and high expression of E2F7 correlated with a shorter median OS and PFS in HCC patients. Cellular functional analysis demonstrated that miRNA-302a/d negatively regulates self-renewal capability and cell cycle entry of liver cancer stem cells via suppression of its target gene E2F7 and its downstream AKT/β-catenin/CCND1 signaling pathway.
Our data provide the first evidence that E2F7 is a direct target of miRNA-302a/d and miRNA-302a/d inhibits the stemness of LCSCs and proliferation of HCC cells by targeting the E2F7/AKT/β-catenin/CCND1 signaling pathway.
Bone is a common site of metastasis in lung cancer, but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by ...digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL receptor 20 subunit beta (IL-20RB) mediated a direct tumoral response to osteoclasts. Tumoral expression of IL-20RB was associated with bone metastasis of lung cancer, and functionally, IL- 20RB promoted metastatic growth of lung cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete the IL20RB ligand IL-19, and IL-19 stimulated IL-20RB-expressing tumor cells to activate downstream JAK1/STAT3 signaling, leading to enhanced proliferation of tumor cells in bone. Importantly, blocking IL-20RB with a neutralizing antibody significantly suppressed bone metastasis of lung cancer. Overall, our data revealed a direct protumor role of osteoclastic niche in bone metastasis and supported IL-20RB-targeting approaches for metastasis treatment.
Osteosarcoma, one of the common malignant tumors in the skeletal system, originates in mesenchymal tissue, and the most susceptible area of occurrence is the metaphysis with its abundant blood ...supply. Tumors are characterized by highly malignant spindle stromal cells that can produce bone-like tissue. Most of the osteosarcoma are primary, and a few are secondary. Osteosarcoma occurs primarily in children and adolescents undergoing vigorous bone growth and development. Most cases involve rapid tumor development and early blood metastasis. In recent years, research has grown in the areas of molecular biology, imaging medicine, biological materials, applied anatomy, surgical techniques, biomechanics, and comprehensive treatment of tumors. With developments in molecular biology and tissue bioengineering, treatment methods have also made great progress, especially in comprehensive limb salvage treatment, which significantly enhances the quality of life after surgery and improves the 5-year survival rate of patients with malignant tumors. This article provides a review of limb salvage, immunotherapy, gene therapy, and targeted therapy from traditional amputation to neoadjuvant chemotherapy, providing a reference for current clinical treatments for osteosarcoma.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide due to its high degree of malignancy, high incidence, and low survival rate. However, the underlying ...mechanisms of hepatocarcinogenesis remain unclear. Long non coding RNA (lncRNA) has been shown as a novel type of RNA. lncRNA by acting as ceRNA can participate in various biological processes of HCC cells, such as tumor cell proliferation, migration, invasion, apoptosis and drug resistance by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can predict the efficacy of treatment strategies for HCC and serve as a potential target for the diagnosis and treatment of HCC. Therefore, lncRNA serving as ceRNA may become a vital candidate biomarker for clinical diagnosis and treatment. In this review, the epidemiology of HCC, including morbidity, mortality, regional distribution, risk factors, and current treatment advances, was briefly discussed, and some biological functions of lncRNA in HCC were summarized with emphasis on the molecular mechanism and clinical application of lncRNA-mediated ceRNA regulatory network in HCC. This paper can contribute to the better understanding of the mechanism of the influence of lncRNA-mediated ceRNA networks (ceRNETs) on HCC and provide directions and strategies for future studies.
Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an ...attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP‐qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR‐433, while dual luciferase assay was carried out to confirm the targeting relationship between miR‐433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo‐tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A‐miR‐433‐FXYD3‐PI3K‐AKT axis in the progression of HCC after loss‐ and gain‐function assays. KDM5A p‐p85 and p‐AKT were highly expressed but miR‐433 was down‐regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR‐433 by demethylating H3K4me3 on its promoterregion. miR‐433 negatively targeted FXYD3. Depleting miR‐433 or re‐expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down‐regulated miR‐433 and up‐regulated FXYD3‐PI3K‐AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3‐PI3K‐AKT axis to enhance angiogenesis in HCC by suppressing miR‐433.
As one of the common cancers that threaten human life, the recurrence and metastasis of colorectal cancer seriously affect the prognosis of patients. Although new drugs and comprehensive treatments ...have been adopted, the current treatment effect on this tumor, especially in advanced colorectal cancer, is still not satisfactory. More and more evidence shows that tumors are likely to be a stem cell disease. In recent years, the rise of cancer stem cell theory has provided a new way for cancer treatment. Studies have found that a small number of special cells in colorectal cancer tissues that induce tumorigenesis, proliferation, and promote tumor migration and metastasis, namely, colorectal cancer stem cells. Colorectal cancer stem cells are defined with a group of cell-surface markers, such as CD44, CD133, CD24, epithelial cell adhesion factor molecule, LGR5, and acetaldehyde dehydrogenase. They are highly tumorigenic, aggressive, and chemoresistant and thus are critical in the metastasis and recurrence of colorectal cancer. Therefore, targeting colorectal cancer stem cells may become an important research direction for the future cure of colorectal cancer.
Display omitted
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is derived from the bacterial innate immune system and engineered as a robust gene-editing tool. Due to the higher ...specificity and efficiency of CRISPR/Cas9, it has been widely applied to many genetic and non-genetic disease, including cancers, genetic hemolytic diseases, acquired immunodeficiency syndrome, cardiovascular diseases, ocular diseases, and neurodegenerative diseases, and some X-linked diseases. Furthermore, in terms of the therapeutic strategy of cancers, many researchers used the CRISPR/Cas9 technique to cure or alleviate cancers through different approaches, such as gene therapy and immune therapy.
of Review.
Here, we conclude the recent application and clinical trials of CRISPR/Cas9 in non-cancerous diseases and cancers and pointed out some of the problems to be solved.
Key Scientific Concepts of Review.
CRISPR/Cas9, derived from the microbial innate immune system, is developed as a robust gene-editing tool and has been applied widely. Due to its high accuracy and efficiency, CRISPR/Cas9 techniques may provide a great chance to treat some gene-related diseases by disrupting, inserting, correcting, replacing, or blocking genes for clinical application with gene therapy.
PDF
