As a non-coding RNA molecule, circular RNAs (circRNAs) have significant specificity, and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer (GC). However, this mechanism has no evidence yet. This article explores the functions of hsa_circRNA_102415 in the malignant behavior and potential downstream signaling of GC cells. The chosen approach is loss of signal and functional gain.

To investigate and analyze the relationship between hsa_circRNA_102415 and GC and explore its specific role. Results provide reference for other researchers to develop targeted treatment plans.

The gene expression omnibus (GEO) database can be used to obtain the microarray dataset GSE83521. Data were analyzed using the GEO2R tool to identify differences in circRNAs between normal and GC samples. Quantitative real-time polymerase chain reaction was used to detect differentially expressed genes in GC tissue samples and adjacent cancer tissue samples. GC cells were transfected with small interfering-hsa_circRNA_104415 and plasmid DNA (pcDNA)-hsa_ircRNA_102415. Multiple detection methods, such as Transwell and cell counting kit 8, were used to evaluate cellular physiological activities, including cell invasion and proliferation. The relationship between Wnt family members 2B, microRNA (miR)-4529-5p, etc., including argonaute 2-RNA immunoprecipitation and luciferase reporter genes was analyzed. Rescue experiments were conducted to analyze and explore the relationship between the malignant behavior of GC cells and hsa_circRNA_102415.

GEO2R analysis confirmed that hsa_circRNA_102415 had significantly higher expression levels in disease tissues. hsa_circRNA_102415 and miR-4529-5p showed a negative correlation in disease cells, suggesting that hsa_circRNA_102415 upregulated WNT2B expression in GC cells as a competing endogenous RNA for miR-4529-5p. miR-4529-5p mimic or small interfering-WNT2B reversed the effects of pcDNA-hsa_circRNA_102415 or miR-4529-5p inhibitor on cell malignant functions.

miR-4529-5p was used to successfully activate the potential of WNT2B, clarify the role of hsa_circRNA_102415 in GC cells, and provide reference for other researchers to develop targeted treatment plans.

Tumor metastasis and poor drug efficacy are two of the most common causes of therapeutic failure in cancer patients. The underlying molecular mechanism requires further exploration, and novel effective curative strategies are urgently needed. Nature is a rich source of novel drugs, and Lycorine hydrochloride (Lyc.HCL) is a natural alkaloid with tremendous therapeutic potential. However, the molecular mechanisms of its antitumor activity are still unknown. In the current study, we investigated the effects and mechanisms of Lyc.HCL against esophageal squamous cell carcinomas (ESCCs), which pose serious threats to human life.

An MTS assay and a clone formation assay were used to assess the viability of ESCC cell lines after Lyc.HCL treatment in vitro. Apoptosis and cell cycle regulation were analyzed using flow cytometry. Wound healing and Transwell assays were used to analyze cell migration, while invasion was analyzed using the Matrigel Transwell assay. We detected the expression of tripartite motif-containing 22 (TRIM22) through immunohistochemistry and Western blotting. A docking experiment was performed to explore the targets of Lyc.HCL. The expression levels of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/extracellular signal-regulated kinase (Erk) pathway components were detected through Western blotting. A rescue experiment was performed to determine the potential role of TRIM22. In addition, we explored the in vivo anti-ESCC effects and mechanism of Lyc.HCL by using it to treat tumor-bearing mice.

The Lyc.HCL treatment was found to inhibit esophageal squamous cell carcinoma cell proliferation both in vitro and in vivo by blocking the cell cycle at the G2 phase, inhibiting cell migration and invasion. We found that the TRIM22 protein was highly expressed in ESCCs but not in normal esophageal tissue. Lyc.HCL directly targeted TRIM22, decreasing the expression of TRIM22 and the JAK2/STAT3 and Erk signaling pathways, both in vitro and in vivo. Using animal experiments, we observed that the depletion of TRIM22 delayed tumor growth, but this effect was significantly reversed upon TRIM22 overexpression.

Taken together, these findings demonstrate that Lyc.HCL can effectively suppress ESCC both in vitro and in vivo by targeting TRIM22 and regulating the JAK2/STAT3 and Erk pathways. These results suggest that Lyc.HCL may serve as a potential novel therapeutic for ESCC, with TRIM22 emerging as a promising target for treatment.

Cervical cancer (CC) is considered a public health problem. Circular RNAs (circRNAs) serve important roles in different types of cancer, including CC. However, the mechanisms used by circRNAs to facilitate CC progression are currently unclear. The present study analyzed the effects of hsa_circ_0009910 knockdown on microRNA (miRNA/miR)-198 and mesenchymal-epithelial transition factor (c-Met) expression levels and its impact on apoptosis and the viability of HeLa cells. Differentially expressed circRNAs in CC were identified using analysis of circRNA microarray data. Bioinformatics analysis was performed to predict circRNA-microRNA (miRNA) and miRNA-mRNA interactions. The knockdown of hsa_circ_0009910 in HeLa cells was performed using small interfering RNA and the expression levels of hsa_circ_0009910, miR-198 and c-Met were assessed using reverse transcription-quantitative PCR. The viability and apoptosis of HeLa cells were evaluated using MTT, neutral red uptake and ApoLive-Glo™ multiplex assays. Hsa_circ_0009910 was significantly upregulated in HeLa cells and the knockdown of hsa_circ_0009910 increased miRNA-198 expression levels, reduced c-Met expression levels and decreased cellular viability, but not apoptosis, in HeLa cells. Overall, these results indicated that hsa_circ_0009910 could act as a molecular sponge of miRNA-198 and contribute to the upregulation of c-Met expression levels. The hsa_circ_0009910/miRNA-198/c-Met interaction network affects the viability, but not apoptosis, of HeLa cells. Based on this mechanism, the present study suggests that hsa_circ_0009910 may be a promising biomarker for CC.

Papillary thyroid cancer (PTC) is the most common thyroid tumor (TC). However, there is still a lack of effective indicators for PTC detection and prognosis. We intended to find a novel tumor marker for the progression of PTC.

The expression of circRNAs was measured by quantitative real-time polymerase chain reaction (qRT-PCR). SiRNA transfection was used to knockdown the expression of hsa_circ_0010023 in K1 cells. Cell proliferation was evaluated using cell counting and CCK8. Cell apoptosis was analyzed using flow cytometry. Hsa_circ_0010023 downstream pathways were predicted with bio-informatics analysis. The miR-1250-5p and MAPK1 were measured by qRT-PCR. The interaction between miR-1250-5p and hsa_circ_0010023 was vertified by dual-luciferase reporter assay.

Among the four circRNAs screened, only hsa_circ_0010023 and hsa_circ_0128482 were highly expressed in PTC (P < 0.05). The expression of hsa_circ_0010023 was significantly correlated with lymph node metastasis and extrathyroid infiltration (P < 0.05). Compared with the control group, the cell proliferation of the si-circ-0010023 group was significantly inhibited (P < 0.05). Knockdown of hsa_circ_0010023 promotes apoptosis of K1 cells (P < 0.001). The expression of hsa_circ_0010023 was negatively correlated with miR-1250-5p and positively correlated with MAPK1. MiR-1250-5p overexpression significantly reduced the luciferase activity of wild type plasmid (hsa_circ_0010023 WT), but not that of mutant type plasmid (hsa_circ_0010023 MUT).

The expression level of hsa_circ_0010023 was positive related to the progression of PTC, and hsa_circ_0010023 may promote PTC through sponging miR-1250-5p. Hsa_circ_0010023 may be a potential bio-marker for the diagnosis of PTC.

This study aimed to explore the molecular mechanism through which circular RNA of ataxin 7 (circATXN7) regulates the proliferation and invasion of esophageal cancer (EC) cells via microRNA (miR)-4319/NLR family CARD domain containing 5 (NLRC5).

The localization of circATXN7 in EC cells was determined by RNA fluorescent in situ hybridization (RNA-FISH). The mRNA levels of circATXN7, miR-4319, and NLRC5 were quantified by reverse transcription-polymerase chain reactions. The binding activity of circATXN7 to miR-4319 was assessed using RNA-binding protein immunoprecipitation. Whether circATXN7 regulates the proliferation of EC cells via miR-4319 was explored using dual-luciferase reporter gene colony formation assays. Protein levels were quantified by western blot. The effect of NLRC5 on the proliferation and invasion of EC cells was examined using colony formation and Transwell assays. A subcutaneous transplanted tumor nude mouse model was established to observe the effect of circATXN7 on the proliferation of EC cells in vivo.

circATXN7 localized mainly to the cytoplasm. Overexpression or inhibition of miR-4319 significantly regulated the proliferation of EC cells, while circATXN7 competitively inhibited miR-4319 expression. Overexpression of miR-4319 significantly inhibited NLRC5 expression, indicating NLRC5 is a downstream regulatory target of miR-4319. circATXN7 influenced NLRC5 expression via miR-4319. In vivo tumor formation experiments in nude mice revealed that knocking down circATXN7 regulated NLRC5 expression via miR-4319 and significantly inhibited the proliferation of EC cells.

In vitro cell and in vivo animal experiments showed that circATXN7 regulates the proliferation, invasion, and migration of EC cells through the miR-4319/NLRC5 signaling pathway.

Non-small cell lung cancer (NSCLC) is typically diagnosed at advanced stages, which limits the effectiveness of therapeutic interventions. The present study aimed to explore the role of the newly identified circLIFRSA in the PTEN/AKT signaling pathway and its involvement in the malignant processes of NSCLC.

CircLIFRSA expression was identified through microarray analysis, and its levels in NSCLC samples were quantified by RT-qPCR. The impact of circLIFRSA on cell growth, proliferation, apoptosis, and cell cycle were evaluated by MTT assay, colony formation assay, and flow cytometry. Additionally, Western blotting was employed to analyze the expression of PTEN and phosphorylated AKT (pAKT) in NSCLC cells.

The expression of circLIFRSA was found to be significantly reduced in NSCLC cells and tissues. This downregulation correlated with various clinicopathological characteristics and indicated its potential as an early diagnostic biomarker for NSCLC. Importantly, circLIFRSA was shown to inhibit cell growth and proliferation while promoting apoptosis in NSCLC cells. Mechanically, circLIFRSA was found to attenuate the malignant processes of NSCLC cells via the miR-1305/PTEN axis and the suppression of AKT phosphorylation.

These findings indicate that circLIFRSA/miR-1305/PTEN axis attenuates malignant processes by regulating AKT phosphorylation, and provide new insights into the potential of circLIFRSA as a biomarker for early diagnosis and as a promising therapeutic target in NSCLC.

Esophageal cancer (EC) is a common form of malignant tumor in the digestive system that is classified into two types: Esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinoma. ESCC is known for its early onset of symptoms, which can be difficult to identify, as well as its rapid progression and tendency to develop drug resistance to chemotherapy and radiotherapy. These factors contribute to the high incidence of disease and low cure rate. Therefore, a diagnostic biomarker and therapeutic target need to be identified for ESCC. Non-coding RNAs (ncRNAs) are a class of molecules that are transcribed from DNA but do not encode proteins. Initially, ncRNAs were considered to be non-functional segments generated during transcription. However, with advancements in high-throughput sequencing technologies in recent years, ncRNAs have been associated with poor prognosis, drug resistance and progression of ESCC. The present study provides a comprehensive overview of the biogenesis, characteristics and functions of ncRNAs, particularly focusing on microRNA, long ncRNAs and circular RNAs. Furthermore, the ncRNAs that could potentially be used as diagnostic biomarkers and therapeutic targets for ESCC are summarized to highlight their application value and prospects in ESCC.

Circular RNA (circRNA) was first observed in the cytoplasm of eukaryotic cells in 1979, but it was not characterized in detail until 2012, when high‑throughput sequencing technology was more advanced and available. Consequently, the mechanism of circRNA formation and its biological function have been progressively elucidated by researchers. circRNA is abundant in eukaryotic cells and exhibits a certain degree of organization, timing and disease‑specificity. Additionally, it is poorly degradable, meeting the characteristics of an ideal clinical biomarker. In the present review, the recent research progress of circRNAs in digestive tract malignant tumors was primarily discussed. This included the roles, biological functions and clinical significance of circRNA, providing references for its research value and clinical potential in gastrointestinal cancer.

Development of new diagnostic methods is essential for disease diagnosis and treatment. In this work, we present a stimuli-responsive incremental DNA machine auto-catalyzed CRISPR-Cas12a (SRI-DNA machine/CRISPR-Cas12a) feedback amplification for ultrasensitive molecular detection of miRNA-21, which is an important biomarker related closely to the initiation and development of cancers, such as esophageal cancer. Strategically, the powerful SRI-DNA machine and efficient trans-cleavage activity of the CRISPR-Cas12a system are ingeniously integrated via a rationally designed probe termed as stem-elongated functional hairpin probe (SEF-HP). The SRI-DNA machine begins with the target miRNA, the trigger of the reaction, binding complementarily to the SEF-HP, followed by autonomously performed mechanical strand replication, cleavage, and displacement circuit at multiple sites. This conversion process led to the amplified generation of numerous DNA activators that are complementary with CRISPR RNA (CrRNA). Once formed the DNA activator/CrRNA heteroduplex, the trans-cleavage activity of the CRISPR-Cas12a was activated to nonspecific cleavage of single-stranded areas of a reporter probe for fluorescence emission. Under optimal conditions, the target miRNA can be detected with a wide linear range and an excellent specificity. As a proof-of-concept, this SRI-DNA machine/CRISPR-Cas12a feedback amplification system is adaptable and scalable to higher-order artificial amplification circuits for biomarkers detection, highlighting its promising potential in early diagnosis and disease treatment.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

Circular RNA (circRNA) can influence the development of hepatocellular carcinoma (HCC) as a competitive endogenous RNA (ceRNA). However, there are still many circRNAs whose functions are unknown. Our research explores the role of a novel circRNA, hsa_circ_0079875, in HCC. The expression of hsa_circ_0079875 in HCC was verified by next-generation sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH). The distribution of hsa_circ_0079875 in HCC cells was investigated by RNA subcellular isolation and FISH assays. The functional effects on HCC proliferation, invasion, migration, cell cycle, and apoptosis were verified by overexpression and knockdown of hsa_circ_0079875. Moreover, xenograft mouse models and immunohistochemistry experiments were used to assess the function of hsa_circ_0079875 in vivo. Hsa_circ_0079875 was up-regulated in HCC tissues and mainly distributed in the cytoplasm. Higher hsa_circ_0079875 leads to larger tumor tissue, more microvascular invasion(MVI) and higher AFP levels, which in turn leads to a poor prognosis. Overexpression of hsa_circ_0079875 can promote the proliferation, migration, and invasion of HCC cells and inhibit apoptosis in vitro and in vivo. Knocking down hsa_circ_0079875 has the opposite effect. Sequencing and biological information predicted the target miRNA and mRNA of hsa_circ_0079875. Further bioinformatics and clinical correlation analysis revealed that hsa_circ_0079875 promote the malignant biological behaviors of HCC through hsa_circ_0079875/miR-519d-59/NRAS ceRNA net. Therefore, hsa_circ_0079875 can be a potential prognostic marker and therapeutic target for HCC.

Gastrointestinal cancers are a huge worldwide health concern, which includes a wide variety of digestive tract cancers. Circular RNAs (circRNAs), a kind of non-coding RNA (ncRNAs), are a family of single-stranded, covalently closed RNAs that have become recognized as crucial gene expression regulators, having an impact on several cellular functions in cancer biology. The gut microbiome, which consists of several different bacteria, actively contributes to the regulation of host immunity, inflammation, and metabolism. CircRNAs and the gut microbiome interact significantly to greatly affect the growth of GI cancer. Several studies focus on the complex functions of circRNAs and the gut microbiota in GI cancers, including esophageal cancer, colorectal cancer, gastric cancer, hepatocellular cancer, and pancreatic cancer. It also emphasizes how changed circRNA expression profiles and gut microbiota affect pathways connected to malignancy as well as how circRNAs affect hallmarks of gastrointestinal cancers. Furthermore, circRNAs and gut microbiota have been recommended as biological markers for therapeutic targets as well as diagnostic and prognostic purposes. Targeting circRNAs and the gut microbiota for the treatment of gastrointestinal cancers is also being continued to study. Despite significant initiatives, the connection between circRNAs and the gut microbiota and the emergence of gastrointestinal cancers remains poorly understood. In this study, we will go over the most recent studies to emphasize the key roles of circRNAs and gut microbiota in gastrointestinal cancer progression and therapeutic options. In order to create effective therapies and plan for the future gastrointestinal therapy, it is important to comprehend the functions and mechanisms of circRNAs and the gut microbiota.

Objectives: Summarize the progress and hot topic evolution of non-coding RNAs (ncRNAs) research in esophageal squamous cell carcinoma (ESCC) in recent years and predict future research directions. Methods: Relevant articles from the Web of Science until 31 October 2023 were obtained. Bibliometric analysis of included articles was performed using software (VOSviewer, CiteSpace, and Bibliometrix). The volume and citation of publications, as well as the country, institution, author, journal, keywords of the articles were used as variables to analyze the research trends and hot spot evolution. Results: 1,118 literature from 2008 to 2023 were retrieved from database, with 25 countries/regions, 793 institutions, 5,426 authors, 261 journals involved. Global cooperation was centered on China, Japan, and the United States. Zhengzhou University, an institution from China, had the highest publication. The most prolific author was Guo Wei, and the most prolific journal was Oncology Letters. Analysis of keywords revealed that the research in this field revolved around the role of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC, mainly including micro RNAs, long non-coding RNAs, and then circular RNAs. Conclusion: Overall, research on ncRNAs in ESCC remains strong. Previous research has mainly focused on the basic research, with a focus on the mechanism of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC. Combining current research with emerging disciplines to further explore its mechanisms of action or shifting the focus of research from preclinical research to clinical research based on diagnosis, treatment, and prognosis, will be the main breakthrough in this field in the future.

Long non-coding RNAs (lncRNAs) play a critical role in the development of ovarian cancer (OC).

The study aimed to determine the role of LncRNA LINC01123 in OC bio-progression, which is upregulated in OC tissues during OC progression.

Bioinformatics methods, GEPIA, and qRT-PCR were used to reveal the level and correlation of LINC01123, hsa-miR-516b-5p, and VEGFA, in OC cell lines. MTT, EdU, TUNEL, and Transwell assays were performed to assess the bioactivity of OC cell. Target sites of LINC01123 and hsa-miR-516b-5p were predicted using Starbase, and the potential linkage points of VEGFA and hsa-miR-516b-5p were predicted using TargetScan. These sites and linkage points were confirmed by double luciferase reporter assay.

LINC01123 was upregulated in OC cell lines and LINC01123 silencing suppressed the proliferation and metastasis of OC cells, but promoted cell apoptosis. hsa-miR-516b-5p was linked to LINC01123 and. VEGFA was downstream of hsa-miR-516b-5p. Importantly, silencing of hsa-miR-516b-5p reversed the inhibitory impact of si-LINC01123. The result of hsa-miR-516b-5p inhibitor + si-LINC01123 co-transfection were rescued by si-VEGFA.

LINC01123 promotes OC development by dampening miR-516b-5p function, and may be a novel target for treating OC.

Circular RNA (circRNA) plays multiple roles in the development of esophageal cancer (EC). Herein, we investigate the function of circ_0001944 in EC progression and the related mechanism. Expression of circ_0001944, microRNA-338-5p (miR-338-5p), pyruvate dehydrogenase kinase 1 (PDK1), E-cadherin and N-cadherin was analyzed by quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry assay. Cell viability, proliferation, apoptosis, invasion and migration were investigated by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell invasion and wound-healing assays, respectively. Glucose consumption was detected by Glucose Assay Kit. Lactate production was analyzed by Lactate Assay Kit. ATP/ADP ratio was determined by ADP/ATP ratio Assay Kit. The associations among circ_0001944, miR-338-5p and PDK1 were identified by dual-luciferase reporter and RNA pull-down assays. Xenograft mouse model assay was used to explore the role of circ_0001944 on tumor tumorigenesis in vivo. Circ_0001944 and PDK1 expression were significantly upregulated, while miR-338-5p was downregulated in EC tissues and cells in contrast with normal esophageal tissues and cells. Circ_0001944 knockdown inhibited EC cell proliferation, invasion, migration and glycolysis but induced apoptosis. Meanwhile, circ_0001944 depletion suppressed tumor tumorigenesis in vivo. Mechanistically, circ_0001944 bound to miR-338-5p, and miR-338-5p targeted PDK1. In addition, miR-338-5p inhibitors attenuated circ_0001944 depletion-induced effects in EC cells. The regulation of miR-338-5p on EC progression involved the downregulation of PDK1. Further, circ_0001944 controlled PDK1 expression through miR-338-5p. Circ_0001944 knockdown inhibited EC development and glycolysis by regulating the miR-338-5p/PDK1 pathway, providing a promising target for EC therapy.

Ovarian cancer is one of the female reproductive system tumors. Chemotherapy is used for advanced ovarian cancer patients; however, drug resistance is a pivotal cause of chemotherapeutic failure. Hence, it is critical to explore the molecular mechanisms of drug resistance of ovarian cancer cells and to ameliorate chemoresistance. Noncoding RNAs (ncRNAs) have been identified to critically participate in drug sensitivity in a variety of human cancers, including ovarian cancer. Among ncRNAs, circRNAs sponge miRNAs and prevent miRNAs from regulation of their target mRNAs. CircRNAs can interact with DNA or proteins to modulate gene expression. In this review, we briefly describe the biological functions of circRNAs in the development and progression of ovarian cancer. Moreover, we discuss the underneath regulatory molecular mechanisms of circRNAs on governing drug resistance in ovarian cancer. Furthermore, we mention the novel strategies to overcome drug resistance via targeting circRNAs in ovarian cancer. Due to that circRNAs play a key role in modulation of drug resistance in ovarian cancer, targeting circRNAs could be a novel approach for attenuation of chemoresistance in ovarian cancer.

The interactions among circRNAs, the PI3K/AKT pathway, and their downstream effectors are intricately linked to their functional roles in tumorigenesis. Furthermore, the circRNAs/PI3K/AKT axis has been significantly implicated in the context of digestive system tumors. This axis is frequently abnormally activated in digestive cancers, including gastric cancer, colorectal cancer, pancreatic cancer, and others. Moreover, the overactivation of the circRNAs/PI3K/AKT axis promotes tumor cell proliferation, suppresses apoptosis, enhances invasive and metastatic capabilities, and contributes to drug resistance. In this regard, gaining crucial insights into the complex interaction between circRNAs and the PI3K/AKT pathway holds great potential for elucidating disease mechanisms, identifying diagnostic biomarkers, and designing targeted therapeutic interventions.

Ranking from seventh in incidence to sixth in mortality, esophageal carcinoma is considered a severe malignancy of food pipe. Later-stage diagnosis, drug resistance, and a high mortality rate contribute to its lethality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two main histological subtypes of esophageal carcinoma, with squamous cell carcinoma alone accounting for more than eighty percent of its cases. While genetic anomalies are well known in esophageal cancer, accountability of epigenetic deregulations is also being explored for the recent two decades. DNA methylation, histone modifications, and functional non-coding RNAs are the crucial epigenetic players involved in the modulation of different malignancies, including esophageal carcinoma. Targeting these epigenetic aberrations will provide new insights into the development of biomarker tools for risk stratification, early diagnosis, and effective therapeutic intervention. This review discusses different epigenetic alterations, emphasizing the most significant developments in esophageal cancer epigenetics and their potential implication for the detection, prognosis, and treatment of esophageal carcinoma. Further, the preclinical and clinical status of various epigenetic drugs has also been reviewed.

Growing empirical evidence shows that circular RNAs (circRNAs) are implicated in tumor pathogenesis. However, little is known about the mechanism by which circRNAs contribute to the progression of adenocarcinoma of the esophagogastric junction (AEG). We conducted RNA high-throughput sequencing and bioinformatic analyses on 22 AEG tissues and their matching healthy gastric mucosal tissues and found that circRNA0007766 may act as a tumor promoter in AEG pathogenesis. BaseScope® in situ hybridization revealed that circRNA0007766 was strongly upregulated in AEG. We then constructed co-expression and ceRNA networks to elucidate the relationships among specific circRNAs, microRNAs (miRNAs), and mRNAs. We also demonstrated that circRNA0007766 acted as the sponge of miR-34c-5p, thereby positively regulating cyclin D1. In vivo and in vitro experiments demonstrated the roles of circRNA0007766 in promoting AEG progression and invasion. AEG tissues are characterized by circRNA0007766 upregulation which is correlated with lymph node metastasis and poor survival. To the best of our knowledge, the present study is one of the first to show that the circRNA0007766/miR-34c-5p/cyclin D1 axis is important in AEG progression. Furthermore, the results of this work imply that circRNA0007766 is potentially a novel AEG biomarker.

Esophageal cancer is one of the most malignant gastrointestinal malignancies. Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. In recent years, with developments in basic medicine, it has been demonstrated that the abnormal expression of circular RNA (circRNA) plays an important role in the progression and prognosis of ESCC. This study explored the role and downstream molecular mechanisms of circ_0046534 in ESCC. We identified circ_0046534, which was found to be highly expressed in ESCC tissues and cells. Moreover, the downregulation of circ_0046534 inhibited the proliferation, migration and invasion of ESCC cells and the growth and metastasis of ESCC tumours in vivo. Dual-luciferase reporter assays showed that circ_0046534 sponged miR-339-5p and inhibited the expression of miR-339-5p. Furthermore, MMP2 was identified to be a direct target of miR-339-5p through bioinformatics analysis. In addition, the knockdown of circ_0046534 inhibited the expression of the downstream target gene matrix metalloproteinase 2 (MMP2) by releasing the adsorption of miR-339-5p. Taken together, this study demonstrated that silencing circ_0046534 inhibited the growth and metastasis of ESCC through the miR-339-5p/MMP2 pathway. Circ_0046534 is expected to serve as a new biomarker and target for ESCC and provide a new direction for its diagnosis and treatment.

Investigation on a competitive endogenous RNA (ceRNA) network attracted lots of attention due its function in cancer regulation. Here, we probed into the possible molecular mechanism of circSSPO/microRNA-6820-5p (miR-6820-5p)/kallikrein-related peptidase 8 (KLK8)/PKD1 network in the esophageal squamous cell carcinoma (ESCC). Following whole-transcriptome sequencing and differential analysis in collected ESCC tissue samples, circRNA-miRNA-mRNA regulatory network affecting ESCC was investigated. After interaction measurement among circSSPO/miR-6820-5p/KLK8/PKD1, their regulatory roles in ESCC cell functions in vitro and xenograft tumor growth and lung metastasis in vivo were analyzed. The bioinformatics prediction and sequencing results screened that circSSPO, miR-6820-5p, KLK8, and PKD1 were associated with ESCC development. In ESCC, miR-6820-5p was expressed at very low levels, while circSSPO, KLK8, and PKD1 were highly expressed. In vitro cell experiments further proved that circSSPO competitively inhibited miR-6820-5p to induce ESCC cell malignant properties. Moreover, knockdown of KLK8 or PKD1 inhibited ESCC cell malignant properties. circSSPO also promoted the tumorigenic and metastasis of ESCC through the upregulation of KLK8 and PKD1 expression in vivo. We found that circSSPO was an oncogenic circRNA that was significantly abundant in ESCC tissues and circSSPO exhibited an oncogenic activity in ESCC by elevating expression of KLK8 and PKD1 through suppressing miR-6820-5p expression.

Oesophageal squamous-cell carcinoma (ESCC) is a malignant tumor of the digestive system with a poor prognosis. Recent studies have shown the promoting effect of hsa_circ_0058063 (circ_0058063) on ESCC, but the potential regulatory mechanisms of circ_0058063 in ESCC remain largely unclear. The levels of circ_0058063, microRNA-4319 (miR-4319) and mRNA of thrombospondin-1 (THBS1) were indicated by quantitative real-time polymerase chain reaction in ESCC tissues and cells. Meanwhile, the level of THBS1 was quantified by western blot analysis. In addition, the cell functions were examined by CCK8 assay, Edu assay, flow cytometry assay and transwell assay. Furthermore, the interplay between miR-4319 and circ_0058063 or THBS1 was detected by dual-luciferase reporter assay. Finally, an in vivo experiment was implemented to confirm the effect of circ_0058063. The level of circ_0058063 and THBS1 were increased, and the miR-4319 level was decreased in ESCC tissues in contrast to that in normal tissues and cells. For functional analysis, circ_0058063 deficiency inhibited cell vitality, cell proliferation, migration and invasion in ESCC cells, whereas promoted cell apoptosis. Moreover, miR-4319 was confirmed to repress the progression of ESCC cells by suppressing THBS1. In mechanism, circ_0058063 acted as a miR-4319 sponge to regulate the level of THBS1. Besides, circ_0058063 knockdown also attenuated tumour growth in vivo. Circ_0058063 facilitates the development of ESCC through increasing THBS1 expression by regulating miR-4319, which also offered an underlying targeted therapy for ESCC treatment.

Cervical cancer is the fourth most common malignant tumors in female worldwide. Cirular RNAs (circRNA) represent a new class of regulatory RNA and play a pivotal role in the carcinogenesis and development of tumors. However, their functions have not been fully elucidated in cervical cancer. In this study, we identified an upregulated circRNA, circ_0001589, both in fresh clinical samples and tissue microarray of cervical cancer. Transwell assay and cell apoptosis assay by flow cytometry demonstrated circ_0001589 promotes epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion, and enhanced cisplatin resistance in vitro. In addition, in nude mice model, circ_0001589 increased the number of lung metastases and recovered xenograft growth from cisplatin treatment in vivo. Mechanistically, RNA pull-down assay, RNA immunoprecipitation, and dual-luciferase reporter assay disclosed that circ_0001589 function as an competing endogenous RNA to sponge miR-1248, which directly target the 3' untranslated region of high mobility group box-B1 (HMGB1). Thereby, circ_0001589 upregulated HMGB1 protein expression and accelerate cervical cancer progression. The rescue experiments also revealed that miR-1248 overexpression or HMGB1 knockdown partially reversed the regulatory functions of circ_0001589 on cell migration, invasion, and cisplatin resistance. In summary, our findings suggest the upregulation of circ_0001589 promoted EMT-mediated cell migration and invasion, and enhanced cisplatin resistance via regulating miR-1248/HMGB1 axis in cervical cancer. These results provided new evidence for understanding the carcinogenesis mechanism and finding new therapeutic target for cervical cancer.

EsophageaL squamous cell carcinoma (ESCC) is one of the most common and lethal tumors, however, its underlying molecular mechanisms are not completely understood and new therapeutic targets are needed. Here, we found that the transcription factor basonuclin 1 (BNC1) was significantly upregulated and closely related to the differentiation and metastasis of ESCC. Furthermore, BNC1, LINC01305, and G-protein pathway suppressor 1 (GPS1) had significant oncogenic roles in ESCC. In addition, in vivo experiments showed that knockdown of BNC1 indeed significantly inhibited the proliferation and metastasis of ESCC. We also revealed the molecular mechanism by which LINC01305 recruits BNC1 to the promoter of GPS1, and then GPS1 could mediate the JNK signaling pathway to promote the proliferation and metastases of ESCC. Taken together, we discovered the novel molecular mechanism by which LINC01305/BNC1 upregulates GPS1 expression to promote the development of ESCC, providing a new therapeutic target for ESCC.

Enhancing research indicatedthat circular RNA (circRNA) acted a critical part in cholangiocarcinoma (CHOL) development. This research aims to discover the role of circRNA SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) in CHOL bio-progression, which has been proved to be downregulated in CHOL tissues. In this study, quantitative reverse transcription polymerase chain reaction was used to reveal the level and linkage of circRNA SMARCA5, miRNA-95-3p and TNF receptor-associated factor 3 gene (TRAF3) in CHOL tissues and cancer cells. The target sites of circRNA SMARCA5 and miRNA-95-3p were forecast by Starbase, and Targetscan was conducted to forecast the potential linkage points of TRAF3 and miRNA-95-3p, and which is affirmed by double luciferase reporter assay. CCK-8 and flow cytometry assay was carried to indicate cell viability. And apoptosis-related protein was counted by caspase3 activity and Western blot assay. CircRNA SMARCA5 was downregulated in CHOL cell lines and cancer samples. Besides, over-expression of SMARCA5 inhibited cell growth and promoted apoptotic rate. Dual-luciferase reporter assays presented that miRNA-95-3p could link with circRNA SMARCA5. Moreover, miRNA-95-3p was discovered highly expressed in CHOL. Interference of miRNA-95-3p repressed cell proliferation and raised the apoptosis. Importantly, TRAF3 was validated to be a downstream of miRNA-95-3p. Strengthen of miRNA-95-3p reversed the inhibitory impact of circRNA SMARCA5-plasmid transfection, and the results of miRNA-95-3p inhibitor were reversed by si-TRAF3. CircRNA SMARCA5 is involved in CHOL development by interosculating miRNA-95-3p/TRAF3 axis and may become a novel approach for treating CHOL.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor worldwide. Circular RNA (circRNA) is of great value in tumorigenesis progression. However, the mechanism of circFNDC3B in ESCC remains to be clarified.

Firstly, the circular characteristics of circFNDC3B were evaluated by Actinomycin D and RNase R measurements. The functions of circFNDC3B in ESCC cells were examined by CCK-8, EdU and flow cytometry. Subsequently, the molecular mechanism of circFNDC3B was explained using luciferase reporter gene detection. Finally, we constructed xenograft model to prove the role of circFNDC3B in vivo.

Our study revealed that circFNDC3B was more stable than its linear RNA and prominently upregulated in ESCC. Functional findings suggested that silencing of circFNDC3B reduced the proliferation and enhanced apoptosis of ESCC cells in vitro. Meanwhile, knockdown of circFNDC3B attenuated tumor progression in vivo. Next, miR-370-3p/miR-136-5p was discovered to bind circFNDC3B. miR-370-3p/miR-136-5p reversed the promotive effect on cell proliferation and the inhibitory effect on cell apoptosis of circFNDC3B. MYO5A was a downstream target of miR-370-3p/miR-136-5p. CircFNDC3B served as a sponge for miR-370-3p/miR-136-5p and alleviated the prohibitory effect of miR-370-3p/miR-136-5p on MYO5A, which accelerated ESCC progression.

circFNDC3B positively adjusted the MYO5A expression via spongy miR-370-3p/miR-136-5p, hence achieving the cancer-promoting effect on ESCC. circFNDC3B was a prospective diagnosis marker for ESCC.

This study aims to investigate the regulatory impact of hsa_circ_0043,603, a circular RNA, on the progression of esophageal squamous cell carcinoma (ESCC), which ranks as the sixth leading cause of global mortality. We evaluated the expression, origin, and localization of hsa_circ_0043,603 in ESCC tumors using qRT-PCR, bioinformatics, and FISH analysis. Functional studies were conducted by manipulating the hsa_circ_0043,603 expression in Eca109 cells through overexpression and silencing plasmids. Additionally, xenografts derived from circ_0043,603-overexpressing Eca109 cells enabled us to investigate tumor growth, proliferation, and apoptosis. Through Starbase analysis, we identified miR-1178-3p as a target of circ_0043,603, which was validated using RIP and luciferase assays. Furthermore, we predicted arylacetamide deacetylase (AADAC) as a target of miR-1178-3p and examined its expression in ESCC tissues using Western blot. Lastly, we performed AADAC silencing and overexpression in Eca109 cells to study their impact on cellular phenotypic features, apoptosis, and their interaction with miR-1178-3p mimics and inhibitors. The low expression of hsa_circ_0043,603 in ESCC tissue was associated with poor prognosis. Overexpression of hsa_circ_0043,603 inhibited ESCC growth, invasion, migration, and proliferation, while promoting apoptosis in vitro and suppressing tumor growth in vivo. hsa_circ_0043,603 achieved these effects by targeting the oncogenic miR-1178-3p. Furthermore, AADAC was identified as a target of miR-1178-3p, and its reduced expression was confirmed in ESCC tissues. Overexpression of AADAC in Eca109 cells resulted in suppressed cell growth, proliferation, migration, and invasion by regulating miR-1178-3p. hsa_circ_0043,603 acts as a sponge for miR-1178-3p, leading to the regulation of AADAC expression and inhibition of ESCC development. These results suggest the potential of hsa_circ_0043,603 as a therapeutic and diagnostic target for ESCC.

Increasing evidence has shown that circular RNAs (circRNAs) interact with RNA-binding proteins (RBPs) and promote cancer progression. However, the function and mechanism of the circRNA/RBP complex in esophageal squamous cell carcinoma (ESCC) are still largely unknown. Herein, we first characterized a novel oncogenic circRNA, circ-FIRRE, by RNA sequencing (Ribo-free) profiling of ESCC samples. Furthermore, we observed marked circ-FIRRE overexpression in ESCC patients with high TNM stage and poor overall survival. Mechanistic studies indicated that circ-FIRRE, as a platform, interacts with the heterogeneous nuclear ribonucleoprotein C (HNRNPC) protein to stabilize GLI2 mRNA by directly binding to its 3'-UTR in the cytoplasm, thereby resulting in elevated GLI2 protein expression and subsequent transcription of its target genes MYC, CCNE1, and CCNE2, ultimately contributing to ESCC progression. Moreover, HNRNPC overexpression in circ-FIRRE knockdown cells notably abolished circ-FIRRE knockdown-mediated Hedgehog pathway inhibition and ESCC progression impairment in vitro and in vivo. Clinical specimen results showed that circ-FIRRE and HNRNPC expression was positively correlated with GLI2 expression, which reveals the clear significance of the circ-FIRRE/HNRNPC-GLI2 axis in ESCC. In summary, our results indicate that circ-FIRRE could serve as a valuable biomarker and potential therapeutic target for ESCC and highlight a novel mechanism of the circ-FIRRE/HNRNPC complex in ESCC progression regulation.

Circular RNAs (circRNAs) are closely associated with the development of breast cancer (BC). In this study, we aimed to clarify how differentially expressed circRNAs affect the development of BC.

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circADAM9, miR-1236-3p and fibroblast growth factor 7 (FGF7). Colony formation, 5-ethynyl-2'-deoxyuridine (EdU), wound healing, transwell, and flow cytometry were used to assess cell proliferation, migration, invasion, and apoptosis. Glucose consumption, lactic acid production and ATP levels were assessed using glycolysis metabolism analysis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to verify the relationship between miR-1236-3p and circADAM9 or FGF7. The roles of cirADAM9 on tumor growth were analyzed using a xenograft tumor model. Ki-67 and FGF7 expression was measured via immunohistochemistry (IHC) assay. Apoptosis-related proteins and exosome markers were detected by western blot.

CircADAM9 was highly expressed in BC cells, and circADAM9 silencing inhibited BC cell proliferation, migration, invasion, and glycolysis, and promoted cell apoptosis. Furthermore, miR-1236-3p inhibition could overturn circADAM9 knockdown-mediated BC inhibition. Moreover, the negative influences of miR-1236-3p overexpression on BC progression were restrained via FGF7 overexpression. CircADAM9 silence also inhibited BC tumor growth in vivo.

CircADAM9 promoted BC development partly by the miR-1236-3p/FGF7 axis, highlighting a potential prognostic biomarker and therapeutic target for BC patients.

Curcumin, a natural polyphenol compound, has been identified as an effective therapeutic agent against cancer that exerts its anti-tumor activities by up/downregulating signaling mediators and modulating various cellular processes, including angiogenesis, autophagy, apoptosis, metastasis, and epithelial-mesenchymal transition (EMT). Since almost 98% of genomic transcriptional production is noncoding RNAs in humans, there is evidence that curcumin exerts therapeutic effects through the alterations of noncoding RNAs in various types of cancers. Circular RNAs (circRNAs) are formed by the back-splicing of immature mRNAs and have several functions, including functioning as miRNA sponges. It has been shown that curcumin modulated various circRNAs, including circ-HN1, circ-PRKCA, circPLEKHM3, circZNF83, circFNDC3B, circ_KIAA1199, circRUNX1, circ_0078710, and circ_0056618. The modulation of these circRNAs targeted the expression of mRNAs and modified various signaling pathways and hallmarks of cancer. In this article, we reviewed the pharmacokinetics of curcumin, its anti-cancer activities, as well as the biology and structure of circRNAs. Our main focus was on how curcumin exerts anti-cancer functions by modulating circRNAs and their target mRNAs and pathways.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported to play regulatory roles in ulcerative colitis (UC). In this study, we aimed to determine the specific roles and action mechanism of the nuclear paraspeckle assembly transcript 1 (NEAT1) in UC.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the lncRNA NEAT1 and miR-493-5p expression levels in patients with UC and healthy volunteers. We determine the forecast linkage points of NEAT1 and miR-493-5p using Starbase and those of miR-493-5p and Rab27A using TargetScan, and further verified them using a double luciferase gene reporter kit. RT-qPCR and Western blot analysis were used to determine the lncRNA NEAT1, miR-493-5p, and Rab27A expression levels in lipopolysaccharide (LPS)-induced Caco-2 cells. Flow cytometry and cell counting kit-8 were used to assess Caco-2 cell viability. Tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-1β levels were determined via an enzyme-linked immunosorbent assay.

Expression levels of NEAT1 were upregulated and those of miR-493-5p were downregualted in 10 ng/mL LPS-treated Caco-2 cells and patients with UC. Dual-luciferase gene reporter assay revealed that miR-493-5p is linked to NEAT1, and Rab27A is a downstream target of miR-493-5p. Overexpression of miR-493-5p inhibited the apoptosis and inflammation in LPS-treated Caco-2 cells. Moreover, downregulation of lncRNA NEAT1 expression also inhibited the apoptosis and inflammation in LPS-treated Caco-2 cells, which was reversed by Rab27A plasmid cotransfection.

Our results revealed that NEAT1 participates in UC progression by inhibiting miR-493-5p expression.

As an anticancer drug, cisplatin is widely used, but its clinical application is restricted due to its severe side effects of ototoxicity. Therefore, this study was dedicated to assessing the benefit of ginsenoside extract, 20(S)-Ginsenoside Rh1 (Rh1), on cisplatin-induced ototoxicity. HEI-OC1 cells and neonatal cochlear explants were cultured. Cleaved caspase-3, TUNEL, and MitoSOX Red were observed in vitro by immunofluorescence staining. CCK8 and LDH cytotoxicity assays were detected to measure cell viability and cytotoxicity. Our results showed that Rh1 significantly increased cell viability, reduced cytotoxicity, and alleviated cisplatin-induced apoptosis. In addition, Rh1 pretreatment decreased the excessive accumulation of intracellular reactive oxygen species. Mechanistic studies indicated that Rh1 pretreatment reversed the increase of apoptotic protein expression, accumulation of mitochondrial ROS, and activation of the MAPK signaling pathway. These results suggested that Rh1 can act as an antioxidant and anti-apoptotic agent against cisplatin-induced hearing loss by suppressing the excessive accumulation of mitochondrial ROS, activation of MAPK signaling pathway and apoptosis.

Evidence indicates that circular RNAs (circRNAs) may play an important role in regulating gene expression by binding to miRNAs through miRNA response elements. circRNAs are formed by back-splicing and have a covalently closed structure. The biogenesis of circRNAs also appears to be regulated by certain cell-specific and/or gene-specific mechanisms, and thus some circRNAs are tissue specific and tumor-expression specific. Furthermore, the high stability and tissue specificity of circRNAs may be of value for early diagnosis, survival prediction and precision medicine. This review summarizes current knowledge regarding the classification and functions of circRNAs and the role of circRNAs in regulating the PI3K/AKT and/or MEK/ERK signaling pathways in digestive tract malignancy tumors.

The objective of this study was to explore the role and mechanism of an abnormally expressed circRNA (hsa_circ_0009128) in the progression of oral squamous cell carcinoma.

We conducted quantitative real-time PCR (qRT-PCR) to assess the expression of hsa_circ_0009128 in 51 paired OSCC tissues and analyzed the correlation between clinical features and aberrant expression of hsa_circ_0009128 in OSCC. CCK-8 assays, colony formation assays, transwell assays, and wound healing assays were used to analyze the effect of hsa_circ_0009128 on cell proliferation and migration. Furthermore, epithelial-mesenchymal transition (EMT)-related proteins were evaluated by Western blotting.

Hsa_circ_0009128 was upregulated in both OSCC tissues and cell lines, and high hsa_circ_0009128 correlated with advanced TNM stage (p = 0.046) and lymph node metastasis (p = 0.018) in OSCC patients. Knockdown of hsa_circ_0009128 inhibited cell proliferation and migration. Mechanistically, hsa_circ_0009128 downregulation decreased EMT in OSCC cells as shown by elevated levels of E-cadherin and decreased N-cadherin, vimentin, and MMP9.

The circRNA hsa_circ_0009128 correlates with malignant progression of OSCC. Hsa_circ_0009128 stimulates proliferation and migration in OSCC cells by targeting MMP9 to activate EMT.

Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues.

Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1, miR-142-5p, and nuclear receptor coactivator-3 (NCOA3) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1β, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits.

CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1. Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1-plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si-NCOA3.

CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.

Esophageal squamous cell carcinoma (ESCC) is a digestive tract malignancy associated with poor clinical outcome. Growing evidence have elucidated that circular RNAs (circRNAs) play important roles in the pathological process of ESCC. However, the detailed mechanisms how circRNAs modulate the development of ESCC remain largely unknown. Our study aimed to decipher the role and mechanism of circ-ATIC (also termed as circRNA_0058063) in regulating the progression of ESCC. We found that circ-ATIC and its host gene ATIC were significantly increased in ESCC tissues and cells compared with the adjacent noncancerous tissues or normal esophagus epithelial cell. Circ-ATIC knockdown substantially reduced proliferation and the number of invaded ESCC cells and retarded EMT process, reflecting by the decreased N-cadherin and elevated E-cadherin. However, the level of host gene ATIC was not changed under circ-ATIC suppression. It was predicted that circ-ATIC could bind to miR-1294 and serve as a sponge RNA. The luciferase reporter assay and RNA immunoprecipitation (RIP) assay confirmed their relations. MiR-1294 was decreased in ESCC tissues and cells, which was reversely correlated with circ-ATIC level. Furthermore, PBX3 was predicted and proved to be a downstream direct target of miR-1294. PBX3 mRNA and protein were obviously upregulated in ESCC tumor tissues and cells. PBX3 overexpression could reverse the suppressive roles of miR-1294 mimics on ESCC proliferation and invasion. In an xenograft nude mice model, stable transfection of sh-circ-ATIC significantly retarded the growth of tumor and suppressed VEGF and Ki67. Collectively, circ-ATIC promoted ESCC proliferation and invasion by regulating miR-1294/PBX3 axis.

Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive. Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly. Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis. Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.

CircRNAs function as pivotal molecules to regulate the malignant development of lung cancer. This study was designed to research the functional role and how it acted in lung cancer progression.

Circ_0000520, microRNA-512-5p (miR-512-5p) and Breast cancer-overexpressed gene 1 (KIAA0100) levels were measured through reverse transcription-quantitative polymerase chain reaction assay. Cell Counting Kit-8 assay and EdU assay were used to examine cell proliferation. Cell cycle and apoptosis were evaluated via flow cytometry. The protein levels were determined using western blot. Cell migration and invasion were assessed by wound healing assay and transwell assay. The circ_0000520 function in vivo was explored by tumor xenograft assay. The molecular interaction was analyzed via Dual-luciferase reporter assay.

Circ_0000520 was obviously upregulated in lung cancer tissues and cells. Silence of circ_0000520 inhibited proliferation, cell cycle progression, migration, invasion and angiogenesis but promoted cell apoptosis. Circ_0000520 downregulation reduced tumor growth of lung cancer in vivo. Circ_0000520 served as a miR-512-5p sponge. The oncogenic function of circ_0000520 was partly achieved by sponging miR-512-5p in lung cancer. KIAA0100 was a target of miR-512-5p and miR-512-5p inhibited the malignant behaviors of lung cancer cells via downregulating KIAA0100. Circ_0000520 targeted miR-512-5p to regulate the level of KIAA0100.

All these data demonstrated that circ_0000520 was able to drive the progression of lung cancer via the mediation of miR-512-5p/KIAA0100 axis. Circ_0000520 might be a potential biomarker for lung cancer.

This study aimed to explore the regulation of miR-27b expression on MET/PI3K/AKT pathway, and to explain its effect on biological functions of DLBCL cells.

The expressions of miR-27b and MET gene in DLBCL cells and normal human B cell lines were determined by qRT-PCR. miR-27b expression in DLBCL cell line Toledo was over-expressed with the cell transfection method. The proliferation of DLBCL cells was determined by MTT. And the invasiveness of DLBCL cells was determined by Transwell. The level of apoptosis in DLBCL cells was determined by ELISA. miR-27b targeting of MET was verified by dual- luciferase reporter assay. The activation of MET/PI3K/AKT pathway and the expression of downstream related proteins were determined by Western blot.

The results showed that miR-27b was poorly expressed in DLBCL cell lines compared with normal human B cell lines, and was associated with its high proliferation, high invasiveness and low apoptosis level. High miR-27b expression can reduce the proliferation and increase the apoptosis level in DLBCL cells. By examining the effect of miR-27b over-expression on the MET/PI3K/AKT pathway, it was found that miR-27b can inhibit the proliferation and invasiveness and promote the apoptosis of DLBCL cells by targeting the inhibition of MET expression and the activation of PI3K/AKT pathway.

miR-27b can inhibit the proliferation and invasiveness of DLBCL cells and promote the apoptosis of the cells by targeting MET/PI3K/AKT pathway.

Circular RNAs (circRNAs) are stable molecules with covalently closed structures that have an irreplaceable role in the occurrence, progression, and even treatment of plenty of cancers. Mammalian/mechanistic target of rapamycin (mTOR) is a key regulator in cancers and plays several biological functions, such as proliferation, migration, invasion, autophagy, and apoptosis.

All data were collected through PubMed and CNKI, using terms including "circRNA," "mTOR," "caner," "signaling pathway," "biomarker," "diagnosis," "treatment." Articles published in Chinese and English were included.

In this review, the expression, function, and mechanism of circRNA-associated mTOR in cancers were described. CircRNA-associated-mTOR can regulate the progression and therapy of a variety of cancers in multiple signaling pathways, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mTOR, mitogen-activated protein kinase (MAPK)/mTOR, and AMP-activated protein kinase (AMPK)/mTOR axis. These cancers including esophageal carcinoma (circLPAR3, ciRS-7), gastric cancer (circNRIP1, hsa_circ_0010882, hsa_circ_0000117, hsa_circ_0072309, and circST3GAL6), colorectal cancer (hsa_circ_0000392, hsa_circ_0084927, hsa_circ_0104631, and circFBXW7), liver cancer (circC16orf62, hsa_circ_100338, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, hsa_circ_0079299, and hsa_circ_0002130), pancreatic cancer (circ-IARS and circRHOBTB3), renal carcinoma (ciRS-7), bladder cancer (circUBE2K), prostate cancer (circMBOAT2 and circ-ITCH), ovarian cancer (circEEF2, circRAB11FIP1, circMYLK, and circTPCN), endometrial cancer (hsa_circ_0002577 and circWHSC1), lung cancer (circHIPK3, hsa_circ_0001666), thyroid cancer (hsa_circ_0007694 and hsa_circ_0008274), glioma (circGFRA1, circ-MAPK4, circPCMTD1, and hsa_circ_0037251), osteosarcoma (circTCF25), leukemia (circ-PRKDC), and breast cancer (hsa_circ_0000199, circUBAP2, and circWHSC1).

Esophageal cancer (EC) is an extremely aggressive malignant tumor. Homeobox A10 (HOXA10) is highly expressed and plays an important role in a variety of tumors. However, the function of HOXA10 in EC remains unclear. In this study, HOXA10 was observed to highly express in EC tissues and cells. Interestingly, the CCK-8 assay, flow cytometry, and colony formation assay confirmed that overexpression of HOXA10 promoted proliferation and suppressed cell apoptosis in EC cells. More importantly, the western blot assay indicated that the phosphorylation levels of ERK and p38 were elevated in EC cells overexpressed HOXA10, indicating that overexpression of HOXA10 activated p38/ERK signaling pathway in EC cells. These findings concluded that HOXA10 aggravated EC progression via activating p38/ERK signaling pathway, providing a potential therapeutic target for EC.