• Colorectal cancer
• Migration
• PSMC2
• Proliferation
• hsa_circ_0007718
• miR-1299

• Humans
• Case-Control Studies
• Cell Transformation, Neoplastic
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/metabolism
• Disease Progression
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• HT29 Cells
• MicroRNAs/metabolism
• Proteasome Endopeptidase Complex/metabolism
• RNA, Circular/metabolism

• Colon cancer stem cells
• EMT
• IL-6/STAT3
• Metastasis
• miR-513b-5p

• A2022375/A2022067 Guandong Medical Research Fund
• 8200100073/8210101308 Guangdong Provincial People's Hospital Research Fund
• Guangdong Provincial People’s Hospital Research Fund

• Breast cancer
• Experimental validation
• Molecular docking
• Network pharmacology
• Polysaccharopeptide

• Humans
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Breast Neoplasms/metabolism
• Female
• Animals
• Mice
• Molecular Docking Simulation
• Cell Proliferation/drug effects
• Network Pharmacology
• Apoptosis/drug effects
• STAT3 Transcription Factor/metabolism
• Xenograft Model Antitumor Assays
• Cell Line, Tumor
• Janus Kinase 2/metabolism
• Proteoglycans/pharmacology
• MCF-7 Cells
• Mice, Nude
• Gene Expression Regulation, Neoplastic/drug effects
• Signal Transduction/drug effects

• 2022-KFZD-2 Open Funds for Shaanxi Provincial Key Laboratory of Infection and Immune Diseases
• 2022-QCYZH-004 Shaanxi Qinchuangyuan traditional Chinese medicine innovation research and development program

• Biomarkers
• Colorectal cancer
• Epigenetics
• Small molecules
• Targeted pathways

• Humans
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Early Detection of Cancer
• Signal Transduction/genetics
• Biomarkers, Tumor/genetics
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/therapy

• Cancer
• Colorectal cancer
• Non-coding RNA
• Review
• STAT3
• Treatment
• Tumorogenesis
• lncRNA
• miRNA

• IGF2BP3
• LINC01133
• epithelial-mesenchymal transition
• microRNA-1299
• pancreatic cancer
• proliferation

• Animals
• Mice
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Mice, Nude
• Cell Line, Tumor
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic
• Cell Movement

• acute myeloid leukemia
• biomarker
• circular RNA (circRNA)
• microRNA
• targeted therapy

• biomarker
• locally advanced colon cancer
• predictive
• prognostic

• Humans
• Colonic Neoplasms/diagnosis
• Colonic Neoplasms/therapy
• Neoadjuvant Therapy
• Survival Rate

• Differentially expressed mRNAs
• Differentially expressed miRNAs
• Functional enrichment
• Intracranial aneurysm
• Weighted gene co-expression network analysis

• Aged
• Animals
• Apoptosis/drug effects
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Chaperonin Containing TCP-1/drug effects
• Colonic Neoplasms/pathology
• Down-Regulation
• Female
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/pharmacology
• Middle Aged
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/pathology
• Tumor Burden
• Up-Regulation
• Xenograft Model Antitumor Assays

Circular RNA is a newly discovered member of non‐coding RNA (ncRNA) and regulates the target gene by acting as a micro‐RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non‐small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ‐WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ‐WHSC1 promoted NSCLC proliferation. circ‐WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ‐WHSC1 could act as a sponge for micro‐RNA‐7 (miR‐7) and regulate the expression of TAB2 (TGF‐beta activated kinase one binding protein two). Inhibition of the circ‐WHSC1/miR‐7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ‐WHSC1 in NSCLC. The research suggests that the circ‐WHSC1/miR‐7/TAB2 axis might be a potential target for NSCLC therapy.

• TAB2
• circ-WHSC1
• miR-7
• non-small cell lung cancer

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20–22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.

• Angiogenesis
• Colorectal cancer
• MiRNA

Hypertension has a complex pathogenesis and symptoms appear in advanced disease. Dysregulation of gene expression regulatory factors like microRNAs has been reported in disease development. Identifying biomarkers which could help understand the pathogenesis and prognosis of hypertension is essential. The study's objective was to investigate microRNA expression profiles according to participant blood pressure status. Next generation sequencing was used to identify microRNAs in the whole blood of 48 body mass index-, smoking- and age-matched normotensive (n = 12), screen-detected hypertensive (n = 16) and known hypertensive (n = 20) female participants. Quantitative reverse transcription polymerase chain reaction was used to validate the next generation sequencing findings in a larger, independent sample of 84 men and 179 women. Using next generation sequencing, 30 dysregulated microRNAs were identified and miR-1299 and miR-30a-5p were the most significantly differentially expressed. Both microRNAs were upregulated in known hypertensives or screen-detected hypertensives compared to the normotensives. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated possible involvement of platelet activation, calcium signaling and aldosterone synthesis pathways. Further validation of miR-1299 and miR-30a-5p using quantitative reverse transcription polymerase chain reaction confirmed sequencing results while yielding new findings. These findings demonstrate microRNA dysregulation in hypertension and their expression may be related to genes and biological pathways essential for blood pressure homeostasis.

• blood pressure
• cardiovascular
• hypertension
• microRNA
• non-coding
• sub-Saharan Africa

• Colorectal cancer
• Epidermal growth factor receptor
• epidermal growth factor receptor-antisense RNA 1
• microRNA‑133b
• signal Transducer and Transcription Activator 3

• SOCS3
• STAT3
• colorectal cancer
• microR-4449

A type of evolutionarily conserved, noncoding, small, endogenous, single-stranded RNA, miRNAs are widely distributed in eukaryotes, where they participate in various biological processes as critical regulatory molecules. miR-1299 has mainly been investigated in cancers. miR-1299 is a tumor suppressor that regulates the expression of its target genes, activating or inhibiting the transcription of genes regulating biological activities including cell proliferation, migration, survival and programmed cell death. miR-1299 has become a hotspot in research of disease mechanisms and biomarkers; elucidation of the regulatory roles of miR-1299 in tumorigenesis, proliferation, apoptosis, invasion, migration and angiogenesis may provide a new perspective for understanding its biological functions as a tumor suppressor.

As key regulatory molecules, microRNAs participate in various biological processes and have become a widespread research focus. This article discusses how the microRNA miR-1299 plays a role as a tumor suppressor and participates in the regulation of tumor pathogenesis. We provide an overview of the role of miR-1299 in tumor diseases and discuss the pathogenesis and regulation mechanisms of miR-1299 in different specific cancers.

• apoptosis
• cancer
• invasion
• miR-1299
• microRNAs
• molecular mechanism
• oncogene
• proliferation
• target protein
• tumor suppressor

• STAT3 transcription factor
• colon cancer
• decoy oligodeoxynucleotides
• drug resistance
• erlotinib

• Genetic algorithm
• MIMO
• Pathway integration
• Support vector regression
• Timescale
• Warburg effect

• cell migration
• epithelial–mesenchymal transition
• metastasis
• miRNA
• oncomiR
• tumor invasiveness
• tumor suppressor miR

Long non-coding RNA (lncRNA) exerts a regulatory role in the occurrence and progression of tumors. This study aimed at probing into the function and mechanism of lncRNA DICER1 antisense RNA 1 (DICER1-AS1) in colorectal cancer (CRC).

The expressions of DICER1-AS1, miR-296-5p and STAT3 mRNA were tested by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay was employed to detect cell proliferation, and Transwell was used to detect cell migration and invasion. In addition, the expressions of apoptosis-related proteins Bax and Bcl2 were detected by Western blot. Interactions between DICER1-AS1 and miR-296-5p, and miR-296-5p and STAT3 were predicted and determined by bioinformatics analysis, luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay.

The expressions of DICER1-AS1 and STAT3 mRNA were significantly up-regulated while miR-296-5p expression was remarkably down-regulated in CRC tissues and cell lines. Over-expression of DICER1-AS1 or transfection of miR-296-5p inhibitors could promote the proliferation, migration and invasion and inhibit apoptosis of CRC cells, whereas knockdown of DICER1-AS1 or transfection of miR-296-5p mimics had the opposite effects. Additionally, DICER1-AS1 could down-regulate miR-296-5p expression via sponging it. DICER1-AS1 also enhanced the expression of STAT3, which was identified as a target gene of miR-296-5p.

DICER1-AS1 acts as an oncogenic lncRNA in CRC via modulating miR-296-5p/STAT3 axis. Our results provide a new direction for the diagnosis and treatment of CRC.

• CRC
• DICER1-AS1
• metastasis
• miR-296-5p
• proliferation

Circular RNAs (circRNAs) have been reported to be involved in regulating the development of breast cancer. Paclitaxel (PTX) can be used for the chemotherapy of breast cancer. The study aimed to explore the role and mechanism of circ_0006528 in PTX-resistant breast cancer progression.

The levels of circ_0006528, microRNA-1299 (miR-1299) and cyclin-dependent kinase 8 (CDK8) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to confirm that the circ_0006528 was a circular RNA. PTX resistance and cell proliferation were determined by Cell counting kit-8 (CCK-8) assay. Cell apoptosis, migration and invasion were analyzed by flow cytometry and Transwell assays, respectively. The levels of all proteins were examined by Western blot. The interaction between circ_0006528 and miR-1299 or CDK8 was predicted by online database confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft mice model was constructed to reveal the role of circ_0006528 on tumor growth in vivo.

Circ_0006528 was significantly up-regulated and miR-1299 was down-regulated in PTX-resistant breast cancer tissues and cells compared with control groups. CDK8 protein expression was dramatically upregulated in PTX-resistant breast cancer tissues and cells as compared to control groups. Loss-of-function experiments revealed that circ_0006528 knockdown decreased IC50 value of PTX and restrained proliferation, migration, invasion and autophagy, whereas induced apoptosis of PTX-resistant breast cancer cells in vitro. The inhibitory effects of sh-circ_0006528 on the progression of PTX-resistant breast cancer cells were reversed by decreasing miR-1299 or increasing CDK8 expression. Furthermore, circ_0006528 could modulate CDK8 expression by sponging miR-1299. Circ_0006528 silencing impeded the growth of PTX-resistant tumors by regulating miR-1299/CDK8 axis in vivo.

Circ_0006528 partially contributed to PTX resistance of breast cancer cells through up-regulating CDK8 expression by sponging miR-1299.

• CDK8
• breast cancer
• circ_0006528
• miR-1299
• paclitaxel resistance

Non-small-cell lung cancer (NSCLC) is one of the most malignant tumors. In which, numerous miRNAs had been reported to participate in the pathogenesis. However, the expression and function of miR-1299 in NSCLC are not clear.

To explore the roles of miR-1299 in NSCLC, we detected the levels of miR-1299 in clinical samples of NSCLC and investigated the role of miR-1299 in the regulation of the NSCLC cells proliferation, metastasis, and EMT. Luciferase reporter assay was employed to verify the target of miR-1299. Additionally, the proliferation, metastasis, and EMT of A549 and H1299 cells were analyzed after the overexpression and knockdown of miR-1299.

We found that the miR-1299 expression negatively corresponded with the clinical stage and overall survival in NSCLC patients. Overexpression of miR-1299 inhibited the migration, invasion, and EMT of A549 and H1975 cells. Meanwhile, we proved that miR-1299 is the sponge of EGFR. Besides, our results suggested that miR-1299 inhibits the progression of NSCLC cells through the PI3K/Akt signal pathway.

We demonstrated that miR-1299 inhibits the progression of NSCLC through the EGFR/PI3K/Akt signal pathway. Therapeutic intervention targeting the miR-1299 may provide a potential strategy for the treatment of NSCLC.

• EGFR
• NSCLC
• PI3K/Akt
• miR-1299

Lung cancer (LC) causes the majority of cancer-related deaths. Circular RNAs (circRNAs) were reported to play roles in cancers by targeting pro- and anti-oncogenic miRNAs. However, the mechanisms of circRNAs in LC progression and their prognostic value of treatment response remain unclear. By using next generation sequencing (NGS) of LC cell lines’ transcriptomes, we identified highly overexpressed hsa_circ_0000190 and hsa_circ_000164 as potential biomarkers. By using the highly sensitive RT-ddPCR method, these circRNAs were shown to be secreted by cell lines and were detected in human blood. Clinical validation by RT-ddPCR was carried out on 272 (231 LC patients and 41 controls) blood samples. Higher hsa_circ_0000190 levels were associated with larger tumor size (p < 0.0001), worse histological type of adenocarcinoma (p = 0.0028), later stage (p < 0.0001), more distant metastatic organs (p = 0.0039), extrathoracic metastasis (p = 0.0004), and poor survival (p = 0.047) and prognosis. Using liquid biopsy-based RT-ddPCR, we discovered the correlation between increased hsa_circ_0000190 plasma level (p < 0.0001) and higher programmed death-ligand 1 (PD-L1) level in tumor (p = 0.0283). Notably, long-term follow-up of the immunotherapy treated cases showed that upregulated plasma hsa_circ_0000190 level correlated with poor response to systemic therapy and immunotherapy (p = 0.0002, 0.0058, respectively). Secretory circRNAs are detectable in blood by LB-based RT-ddPCR and may serve as blood-based biomarkers to monitor disease progression and treatment efficacy.

• circular RNA
• droplet digital PCR
• liquid biopsy
• lung cancer
• programmed death-ligand 1

Ovarian cancer (OC) is a big threat for public health. However, the molecular mechanism underlying OC development and progression remains unclear. Although the importance of lncRNA in cancer has been proven, how lncRNA is involved in OC is waiting for further investigation.

qRT-PCR was performed to test expression level. CCK8 and colony formation were conducted to analyze proliferation. Transwell was conducted to measure migration and invasion. Luciferase reporter assay and pulldown assay were utilized to validate RNA interaction.

lncRNA RHPN1-AS1 was highly expressed in OC tissues. RHPN1-AS1 was positively correlated with OC progression and its high expression indicated a low survival rate. Moreover, knockdown of RHPN1-AS1 significantly inhibited the proliferation, migration and invasion of OC cells, and bioinformatics analysis identified that miR-1299 was sponged by RHPN1-AS1 in OC cells. Knockdown of RHPN1-AS1 markedly promoted miR-1299 expression. Of note, inhibition of miR-1299 reversed the roles of RHPN1-AS1 silencing on suppressing proliferation, migration and invasion.

Our study demonstrates that RHPN1-AS1 promotes OC progression via sponging miR-1299, suggesting RHPN1-AS1 may be a novel therapeutic target.

• RHPN1-AS1
• invasion
• miR-1299
• ovarian cancer
• proliferation

• 2016009 Key Subjects of Ningbo No.2 Hospital

Cholangiocarcinoma (CCA) is a highly malignant carcinoma with high mortality rate worldwide. Emerging evidence indicates that aberrantly expressed circular RNAs (circRNAs) functions crucial roles in tumor progression. In this work, we focused on a novel circRNA, circ_0005230, in carcinogenesis and development of CCA. Circ_0005230 levels in CCA specimens and cells were measured by qRT-PCR. The clinical implication of circ_0005230 was analyzed by fisher’s exact test. Gain/loss of-function assays were conducted to reveal the effects of circ_0005230 on the cell proliferation, apoptosis, migration and invasion of CCA cells. Xenograft and lung metastatic models were constructed to confirm the in vitro data. Dual luciferase reporter and rescue assays were carried out to illuminate the mechanism behind the regulatory actions. As data showed, circ_0005230 was elevated in tumors and CCA cells. Its expression in tumor samples was related to clinical severity. Functionally, circ_0005230 significantly facilitated cell growth, clone-forming ability and metastatic properties and inhibit cell apoptosis in CCA cells. The in vivo study further validated the in vitro results. However, knockdown of circ_0005230 did not affect normal biliary epithelial (HIBEC) cell growth and apoptosis. For the mechanism investigation, circ_0005230 could directly sponge miR-1238 and miR-1299 to exert its oncogenic functions. Overall, this work showed that circ_0005230 might act as an effective therapeutic target for CCA.

• cholangiocarcinoma
• circ_0005230
• circular RNA
• miR-1238
• miR-1299

• CeRNA
• RNA sequencing
• laryngeal carcinoma
• lncRNA
• noncoding RNA

• FLT3-ITD(+)acute myeloid leukemia
• KEGG
• S100A7A
• hsa_circ_0000370
• miR-1299

Early-onset colorectal cancer (EOCRC) is an increasing and worrisome entity. The aim of this study was to analyze its association with polyps concerning prognosis and surveillance. EOCRC cases were compared regarding the presence or absence of associated polyps (clinical and molecular features), during a minimum of 7 years of follow-up. Of 119 cases, 56 (47%) did not develop polyps (NP group), while 63 (53%) did (P group). The NP group showed a predominant location of the CRC in the rectum (50%), of sporadic cases (54%), and diagnosis at advanced stages: Only P53 and SMARCB1 mutations were statistically linked to this group. The P group, including mainly early-diagnosed tumors, was linked with the most frequent and differential altered chromosomal regions in the array comparative genomic hybridization. The two most frequent groups according to the follow-up were the NP group (40%), and patients developing polyps in the first 5 years of follow-up (P < 5FU) (34%) (these last groups predominantly diagnosed at the earliest stage and with adenomatous polyps (45%)). EOCRC with polyps that developed during the entire follow-up (PDFU group) were mainly located in the right colon (53%), diagnosed in earlier stages, and 75% had a familial history of CRC. Patients developing polyps after the first 5 years (P > 5FU) showed a mucinous component (50%). Our results show that the absence or presence of polyps in EOCRC is an important prognostic factor with differential phenotypes. The development of polyps during surveillance shows that it is necessary to extend the follow-up time, also in those cases with microsatellite-stable EOCRC.

• early-onset colorectal cancer
• follow-up
• polyp development
• prognosis

Molecular mechanisms associated with inflammation-promoted tumorigenesis have become an important topic in cancer research. Various abnormal epigenetic changes, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, occur during the transformation of chronic inflammation into colorectal cancer (CRC). These changes not only accelerate transformation but also lead to cancer progression and metastasis by activating carcinogenic signaling pathways. The NF-κB and STAT3 signaling pathways play a particularly important role in the transformation of inflammation into CRC, and both are critical to cellular signal transduction and constantly activated in cancer by various abnormal changes including epigenetics. The NF-κB and STAT3 signals contribute to the microenvironment for tumorigenesis through secretion of a large number of pro-inflammatory cytokines and their crosstalk in the nucleus makes it even more difficult to treat CRC. Compared with gene mutation that is irreversible, epigenetic inheritance is reversible or can be altered by the intervention. Therefore, understanding the role of epigenetic inheritance in the inflammation-cancer transformation may elucidate the pathogenesis of CRC and promote the development of innovative drugs targeting transformation to prevent and treat this malignancy. This review summarizes the literature on the roles of epigenetic mechanisms in the occurrence and development of inflammation-induced CRC. Exploring the role of epigenetics in the transformation of inflammation into CRC may help stimulate futures studies on the role of molecular therapy in CRC.

• Colorectal cancer
• Inflammation
• DNA methylation
• Histone modification
• LncRNA
• MicroRNAs
• Epigenetics

• Cell Transformation, Neoplastic/genetics
• Colon/immunology
• Colon/pathology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/pathology
• Disease Progression
• Epigenesis, Genetic/immunology
• Gene Expression Regulation, Neoplastic/immunology
• Humans
• Inflammation/genetics
• Inflammation/immunology
• Inflammation/pathology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/pathology
• Rectum/immunology
• Rectum/pathology
• Tumor Microenvironment/genetics
• Tumor Microenvironment/immunology

• Janus kinases
• MicroRNAs
• cancer
• signal transducer and activator of transcription 3 signaling pathway
• suppressor of cytokine signaling