• APOBECs
• Deamidation
• Oncology diagnosis and treatment
• Physiological functions
• Tumorigenesis

Esophageal squamous cell carcinoma (ESCC) is correlated with worse clinical prognosis and lacks available targeted therapy. Thus, identification of reliable biomarkers is required for the diagnosis and treatment of ESCC.

We downloaded the GSE53625 dataset as a training dataset to screen differentially expressed RNAs (DERs) with the criterion of false discovery rate (FDR) < 0.05 and |log₂fold change (FC)| > 1. A support vector machine classifier was used to find the optimal feature gene set that could conclusively distinguish different samples. An eight-lncRNA signature was identified by random survival forest algorithm and multivariate Cox regression analysis. The RNA sequencing data from The Cancer Genome Atlas (TCGA) database were used for external validation. The predictive value of the signature was assessed using Kaplan–Meier test, time-dependent receiver operating characteristic (ROC) curves, and dynamic area under the curve (AUC). Furthermore, a nomogram to predict patients’ 3-year and 5-year prognosis was constructed. CCK-8 assay, flow cytometry, and transwell assay were conducted in ESCC cells.

A total of 1136 DERs, including 689 downregulated mRNAs, 318 upregulated mRNAs, 74 downregulated lncRNAs and 55 upregulated lncRNAs, were obtained in the GES53625 dataset. From the training dataset, we identified an eight-lncRNA signature, (ADAMTS9-AS1, DLX6-AS1, LINC00470, LINC00520, LINC01497, LINC01749, MAMDC2-AS1, and SSTR5-AS1). A nomogram based on the eight-lncRNA signature, age, and pathologic stage was developed and showed good accuracy for predicting 3-year and 5-year survival probability of patients with ESCC. Functionally, knockdown of LINC00470 significantly suppressed cell proliferation, G1/S transition, and migration in two ESCC cell lines (EC9706 and TE-9). Moreover, knockdown of LINC00470 downregulated the protein levels of PCNA, CDK4, and N-cadherin, while upregulating E-cadherin protein level in EC9706 and TE-9 cells.

Our eight-lncRNA signature and nomogram can provide theoretical guidance for further research on the molecular mechanism of ESCC and the screening of molecular markers.

The online version contains supplementary material available at 10.1186/s11658-022-00331-x.

• Esophageal squamous cell carcinoma
• Long noncoding RNA
• Nomogram
• Signature

In recent years, there has been significant progress in the diagnosis and treatment of esophageal cancer. However, owing to the lack of early diagnosis strategies and treatment targets, the prognosis of patients with esophageal cancer remains unsatisfactory. There is an urgent need to identify novel biomarkers and treatment targets for esophageal cancer. With the development of genomics, long-chain non-coding RNAs (LncRNAs), which were once considered transcriptional “noise,” are being identified and characterized rapidly in large numbers. Recent research shows that LncRNAs are closely related to a series of steps in tumor development and play an important regulatory role in DNA replication, transcription, and post-transcriptional regulation. The abnormal expression of LncRNAs leads to tumor cell proliferation, migration, invasion, and treatment resistance. This review focuses on the latest progress in research on the abnormal expression and functional mechanisms of LncRNAs in esophageal cancer. Further, it discusses the potential applications of these findings towards achieving an early diagnosis, improving treatment efficacy, and evaluating the prognosis of esophageal cancer.

• biomarkers
• esophageal cancer (EC)
• genomics
• long non-coding RNA
• molecular mechanism

Epithelial-mesenchymal transition (EMT) is significantly associated with the invasion and development of esophageal squamous cell carcinoma (ESCC). However, the importance of EMT-related long noncoding RNA (lncRNA) is little known in ESCC.

GSE53624 (N = 119) and GSE53622 (N = 60) datasets retrieved from the Gene Expression Omnibus (GEO) database were used as training and external validation cohorts, respectively. GSE53624 and GSE53622 datasets were all sampled from China. Then, the prognostic value of EMT-related lncRNA was comprehensively investigated by weighted coexpression network analysis (WGCNA) and COX regression model.

High expression of PLA2G4E-AS1, AC063976.1, and LINC01592 significantly correlated with the favorable overall survival (OS) of ESCC patients, and LINC01592 had the greatest contribution to OS. Importantly, ESCC patients were divided into low- and high-risk groups based on the optimal cut-off value of risk score estimated by the multivariate COX regression model of these three lncRNA. Patients with high risk had a shorter OS rate and restricted mean survival time (RMST) than those with low risk. Moreover, univariate and multivariate COX regression revealed that risk stratification, age, and TNM were independent prognostic predictors, which were used to construct a nomogram model for individualized and visualized prognosis prediction of ESCC patients. The calibration curves and time-dependent ROC curves in the training and validation cohorts suggested that the nomogram model had a good performance. Interestingly, clear trends indicated that risk score positively correlated with tumor microenvironment (TME) scores and immune checkpoints TIGIT, CTLA4, and BTLA. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that PLA2G4E-AS1, AC063976.1, and LINC01592 were primarily associated with TNF signaling pathway, NF-kappa B signaling pathway, and ECM-receptor interaction.

We developed EMT-related lncRNA PLA2G4E-AS1, AC063976.1, and LINC01592 for prognostic prediction and risk stratification of Chinese ESCC patients, which might provide deep insight for personalized prognosis prediction in Chinese ESCC patients and be potential biomarkers for designing novel therapy.

• Biomarker
• Drug resistance
• Early diagnosis
• Esophageal cancer
• Noncoding RNA
• Targeted therapy

• Animals
• Biomarkers, Tumor/genetics
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/therapy
• Gene Expression Regulation, Neoplastic
• Humans
• RNA, Long Noncoding/genetics

• Grant No. 81970481 National Natural Science Foundation of China
• 82000514 National Natural Science Foundation of China
• Grant No. 81602627 National Natural Science Foundation of China (CN)
• Grant No. 2018HH0150 Department of Science and Technology of Sichuan Province
• Grant No. 2017GH00072 Chengdu Science and Technology Bureau Program (CN)
• Grant No. ZYJC18010 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University
• 2020HXFH047 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University
• 2020-025 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University
• 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University

Cancer is caused by the rapid and uncontrolled growth of cells that eventually lead to tumor formation. Genetic and epigenetic alterations are among the most critical factors in the onset of carcinoma. Phytochemicals are a group of natural compounds that play an essential role in cancer prevention and treatment. Long non-coding RNAs (lncRNAs) are potential therapeutic targets of bioactive phytochemicals, and these compounds could regulate the expression of lncRNAs directly and indirectly. Here, we critically evaluate in vitro and in vivo anticancer effects of phytochemicals in numerous human cancers via regulation of lncRNA expression and their downstream target genes.

Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play an essential role in various cellular activities, such as differentiation, proliferation, and apoptosis. Dysregulation of lncRNAs serves a fundamental role in the progression and initiation of various diseases, including cancer. Precision medicine is a suitable and optimal treatment method for cancer so that based on each patient’s genetic content, a specific treatment or drug is prescribed. The rapid advancement of science and technology in recent years has led to many successes in this particular treatment. Phytochemicals are a group of natural compounds extracted from fruits, vegetables, and plants. Through the downregulation of oncogenic lncRNAs or upregulation of tumor suppressor lncRNAs, these bioactive compounds can inhibit metastasis, proliferation, invasion, migration, and cancer cells. These natural products can be a novel and alternative strategy for cancer treatment and improve tumor cells’ sensitivity to standard adjuvant therapies. This review will discuss the antineoplastic effects of bioactive plant secondary metabolites (phytochemicals) via regulation of expression of lncRNAs in various human cancers and their potential for the treatment and prevention of human cancers.

• cancer treatment
• lncRNAs
• natural products
• phytochemicals
• precision medicine
• targeted therapy

Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system with high incidence and mortality rate worldwide. Therefore, exploring the pathogenesis of EC and searching for new targeted therapies are the current research hotspot for EC treatment. Long non‐coding RNAs (lncRNAs) are endogenous RNAs with more than 200 nucleotides, but without protein‐coding function. In recent years, lncRNAs have gradually become the focuses in the field of non‐coding RNA. Some lncRNAs have been proved to be closely related to the pathogenesis of EC. Many lncRNAs are abnormally expressed in EC and participate in many biological processes including cell proliferation, apoptosis, and metastasis by inhibiting or promoting target gene expression. LncRNAs can also regulate the progression of EC through epithelial‐mesenchymal transformation (EMT), which is closely related to the occurrence, development, and prognosis of EC. In this article, we review and discuss the involvement of lncRNAs in the progression of EC.

• apoptosis
• biomarker
• diagnosis
• drug resistance
• esophageal cancer
• long non-coding RNA
• metastasis
• prognosis
• proliferation

Evidence from previous studies showed that the dysregulation of microRNA (miR) is frequently associated with tumor progression. The aberrant miR‐210 expression has been identified in a variety of tumors. However, its biological roles in esophageal squamous cell carcinoma (ESCC) still need further elucidation. Thus, in the current study we explore the roles of miR‐210 in ESCC progression. The findings of our study reveal that miR‐210 is down‐regulated in ESCC, which indicates poor prognosis and aggressive tumor progression. Moreover, miR‐210 restoration was found to enhance ESCC viability, invasion, and migration abilities. F‐Box only protein 31 (FBXO31) was confirmed to be one of the targets of miR‐210 in ESCC cells. Results also revealed that miR‐210 played crucial roles in regulating ESCC cell epithelial‐mesenchymal transition (EMT) and Wnt/β‐catenin signaling. In conclusion, data show that miR‐210 serves as an anti‐ESCC miR via down‐regulation of FBXO31 and regulation of EMT and Wnt signaling, suggesting that the miR‐210/FBXO31 axis may function as promising therapeutic targets and effective prognostic markers for ESCC patients.

miR‐210 serves as an anti‐ESCC miR via down‐regulation of FBXO31 and regulation of EMT and Wnt signaling

• Epithelial-mesenchymal transition
• Esophageal squamous cell carcinoma
• F-Box only protein 31
• Wnt/β-catenin
• miR-210

Several studies have reported a prognostic role of the long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) in various cancer types, but its clinical significance has remained inconclusive. The aim of the present meta-analysis was to evaluate the impact of CASC9 expression on the prognosis and clinicopathological features of patients with cancer patients. The PubMed, Embase, Cochrane Library and Web of Science databases were searched for relevant literature and eight studies, including 565 patients with cancer, were selected. The quality of these studies was appraised with the Newcastle-Ottawa Scale (NOS) and the association between CASC9 expression and prognosis or clinicopathological features was analyzed. Patients with high expression levels of CASC9 in their tumor tissues had a lower overall survival rate compared with those in the low CASC9 expression group (hazard ratio=2.25, 95% CI: 1.60-3.17, P<0.001). Furthermore, elevated CASC9 expression was significantly associated with deeper tumor invasion [odds ratio (OR)=2.66, 95% CI: 1.72-4.14, P<0.001], poor tumor differentiation (OR=2.44, 95% CI: 1.24-4.78, P=0.009), lymph node metastasis (OR=3.42, 95% CI: 1.98-5.92, P<0.001) and advanced clinical stage (OR=3.21, 95% CI: 2.21-4.66, P<0.001). In conclusion, CASC9 is a promising biomarker for predicting the prognosis of cancer patients and should be validated in the clinic.

• CASC9
• cancer
• long non-coding RNA
• meta-analysis
• prognosis

• bladder cancer
• cancer susceptibility candidate 9
• enhancer of zeste homolog 2
• phosphatase and tensin homolog
• signal transducer and activator of transcription 3

• Bladder cancer
• CASC9
• FZD6
• lncRNA
• miR-497-5p

• Small cell lung cancer (SCLC)
• chemotherapy insensitivity
• long noncoding RNAs (lncRNAs)
• microRNAs (miRNAs)

The incidence of tongue squamous cell carcinoma (TSCC) has increased in recent decades. However, the function of long non-coding RNA (lncRNA) CASC9 in the occurrence and progression of TSCC is unclear. In this work, we attempted to clarify the role of lncRNA CASC9 in determining the phenotype of TSCC cells, and to clarify the underlying mechanisms.

We used qRT-PCR analysis to identify the level of CASC9 mRNA expression in TSCC clinical samples and cell lines. We investigated cell proliferation, and cell migration and invasion of TSCC cells transfected with siCASC9 or siNC using CCK-8 and transwell assays. Bioinformatics analysis and a luciferase reporter assay were employed to predict and verify the target microRNA (miRNA).

CASC9 was up-regulated in the TSCC tissues and cells, and predicted a poor prognosis. CASC9 silencing significantly inhibited cell proliferation, migration, and invasion of the TSCC cells compared with the non-targeting control small interfering RNA (siCtrl) treatment. miR-423-5p was predicted as the targeting miRNA of CASC9; this was verified by a luciferase reporter assay. CASC9 expression showed a negative correlation with miR-423-5p expression and a positive correlation with SOX12 expression. The miR-423-5p inhibitor can rescue the carcinogenesis effect of CASC9 on TSCC cells.

Our work indicates that CASC9 plays a role in TSCC tumorigenesis; this novel information will improve TSCC molecular targeting therapy.

• CASC9
• invasion
• miR-423-5p
• migration
• proliferation
• tongue squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.

• ESCC
• circRNAs
• lncRNAs
• miRNAs
• ncRNA

• Competing endogenous RNA
• Gene Ontology
• Hepatocellular carcinoma
• Kyoto Encyclopedia of Genes and Genomes
• LncRNA cancer susceptibility candidate 9
• Prognosis

• Biomarkers, Tumor/blood
• Biomarkers, Tumor/metabolism
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/mortality
• Case-Control Studies
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Healthy Volunteers
• Humans
• Kaplan-Meier Estimate
• Liver/pathology
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Liver Neoplasms/genetics
• Liver Neoplasms/mortality
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Predictive Value of Tests
• RNA, Long Noncoding/blood
• RNA, Long Noncoding/metabolism
• ROC Curve
• Survival Rate

• CASC9
• HIF-1α
• cell proliferation
• lung cancer
• metastasis

• Biomarker
• Bladder cancer
• CASC9
• HNSCC
• HOTAIR
• Head-and-neck carcinoma
• Long non-coding RNA
• Squamous cell carcinoma

The cancer susceptibility candidate 9 (CASC9) gene has been reported to exert an oncogenic effect in several types of cancer. However, its role in lung squamous cell carcinoma (LUSC) is unknown. Therefore, the present study examined the expression of CASC9 in LUSC and non-cancer tissues by reverse transcription-quantitative polymerase chain reaction assays and by data mining of high-throughput public databases, including The Cancer Genome Atlas, the Gene Expression Omnibus, ArrayExpress and the Cancer Cell Line Encyclopedia. In vitro experiments were conducted to investigate the effects of CASC9 on the viability and the proliferation of LUSC cells. Furthermore, consulting the alteration status of CASC9 in LUSC from cBioPortal, functional enrichment analysis of co-expressed genes, prediction of potential transcription factors, and inspection of adjacent protein-coding genes were conducted to explore the potential molecular mechanism of CASC9 in LUSC. The results revealed that CASC9 was overexpressed in LUSC tissue, and significantly associated with the malignant progression of LUSC. In vitro experiments demonstrated that CASC9 knockdown by RNA interference attenuated the viability and proliferation of LUSC cells. Multiple copies of CASC9 gene were detected in 4 of 179 available sequenced LUSC cases. A functional enrichment analysis of 200 co-expressed genes indicated that these genes were significantly associated with terms, including 'cell-cell junction organization', 'desmosome organization', 'epidermis development', 'Hippo signaling pathway', 'pathogenic Escherichia coli infection' and 'PID HIF1 TF pathway'. Three genes, Fos-related antigen 2 (FOSL2), SWI/SNF complex subunit SMARCC2, and transcription factor COE1 (EBF1), were predicted by lncRNAMap to be associated with CASC9. Among these, the expression of FOSL2 and EBF1 was positively and negatively correlated with the expression of CASC9, respectively. Two adjacent protein-coding genes, cysteine-rich secretory protein LCCL domain-containing 1 and hepatocyte nuclear factor 4-γ, were also positively correlated with CASC9 expression. In conclusion, the present data suggest that CASC9 serves as an oncogene in LUSC and may be a promising target for alternative therapeutic options for patients with this condition.

• CASC9
• Nrg1
• cell migration
• hemangioma
• invasion
• miR-125a-3p

Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers and effective prognostic indicators for metastasis and recurrence has resulted in the poor prognosis of EC. In addition, the underlying molecular mechanisms of EC development have yet to be elucidated. Accumulating evidence has demonstrated that lncRNAs play a vital role in the pathological progression of EC. LncRNAs may regulate gene expression through the recruitment of histone-modifying complexes to the chromatin and through interactions with RNAs or proteins. Recent evidence has demonstrated that the dysregulation of lncRNAs plays important roles in the proliferation, metastasis, invasion, angiogenesis, apoptosis, chemoradiotherapy resistance, and stemness of EC, which suggests potential clinical implications. In this review, we highlight the emerging roles and regulatory mechanisms of lncRNAs in the context of EC and discuss their potential clinical applications as diagnostic and prognostic biomarkers.

• Application
• Biomarker
• Esophageal cancer
• Long non-coding RNA
• Mechanism