Lung adenocarcinoma (LUAD) has been the major cause of tumor-associated mortality in recent years and has a poor prognosis. Pyroptosis is regulated via the activation of inflammasomes and participates in tumorigenesis. However, the effects of pyroptosis-related lncRNAs (PRlncRNAs) on LUAD have not yet been completely elucidated. Therefore, we attempted to systematically explore patterns of cell pyroptosis to establish a novel signature for predicting LUAD survival. Based on TCGA database, we set up a prognostic model by incorporating PRlncRNAs with differential expression using Cox regression and LASSO regression. Kaplan-Meier analysis was conducted to compare the survival of LUAD patients. We further simplified the risk model and created a nomogram to enhance the prediction of LUAD prognosis. Altogether, 84 PRlncRNAs with differential expression were discovered. Subsequently, a new risk model was constructed based on five PRlncRNAs, GSEC, FAM83A-AS1, AL606489.1, AL034397.3 and AC010980.2. The proposed signature exhibited good performance in prognostic prediction and was related to immunocyte infiltration. The nomogram exactly forecasted the overall survival of patients and had excellent clinical utility. In the present study, the five-lncRNA prognostic risk signature and nomogram are trustworthy and effective indicators for predicting the prognosis of LUAD.

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2021.1972078

A novel pyroptosis-related lncRNA signature for prognostic prediction in patients with lung adenocarcinoma.

Abstract RNA modifications have become hot topics recently. By influencing RNA processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune cell abnormality in human diseases is also a research focus and progressing rapidly these years. Studies have demonstrated that RNA modifications participate in the multiple biological processes of immune cells, including development, differentiation, activation, migration, and polarization, thereby modulating the immune responses and are involved in some immune related diseases. In this review, we present existing knowledge of the biological functions and underlying mechanisms of RNA modifications, including N 6 -methyladenosine (m 6 A), 5-methylcytosine (m 5 C), N 1 -methyladenosine (m 1 A), N 7 -methylguanosine (m 7 G), N 4 -acetylcytosine (ac 4 C), pseudouridine (Ψ), uridylation, and adenosine-to-inosine (A-to-I) RNA editing, and summarize their critical roles in immune cell biology. Via regulating the biological processes of immune cells, RNA modifications can participate in the pathogenesis of immune related diseases, such as cancers, infection, inflammatory and autoimmune diseases. We further highlight the challenges and future directions based on the existing knowledge. All in all, this review will provide helpful knowledge as well as novel ideas for the researchers in this area. 

https://www.nature.com/articles/s41392-022-01175-9.pdf

RNA modifications: importance in immune cell biology and related diseases

Background: Lung adenocarcinoma (LUAD), the major subtype of lung cancer, is among the leading cause of cancer-related death worldwide. Energy-related metabolic reprogramming metabolism is a hallmark of cancer shared by numerous cancer types, including LUAD. Nevertheless, the functional pathways and molecular mechanism by which FAM83A-AS1 acts in metabolic reprogramming in lung adenocarcinoma have not been fully elucidated. Methods: We used transwell, wound-healing scratch assay, and metabolic assays to explore the effect of FAM83A-AS1 in LUAD cell lines. Western blotting, Co-IP assays, and ubiquitination assays were used to detect the effects of FAM83A-AS1 on HIF-1α expression, degradation, and its binding to VHL. Moreover, an in vivo subcutaneous tumor formation assay was used to detect the effect of FAM83A-AS1 on LUAD. Results: Herein, we identified FAM83A-AS1 as a metabolism-related lncRNA, which was highly correlated with glycolysis, hypoxia, and OXPHOS pathways in LUAD patients using bioinformatics analysis. In addition, we uncovered that FAM83A-AS1 could promote the migration and invasion of LUAD cells, as well as influence the stemness of LUAD cells in vivo and vitro. Moreover, FAM83A-AS1 was shown to promote glycolysis in LUAD cell lines in vitro and in vivo, and was found to influence the expression of genes related to glucose metabolism. Besides, we revealed that FAM83A-AS1 could affect glycolysis by regulating HIF-1α degradation. Finally, we found that FAM83A-AS1 knockdown could inhibit tumor growth and suppress the expression of HIF-1α and glycolysis-related genes in vivo. Conclusion: Our study demonstrates that FAM83A-AS1 contributes to LUAD proliferation and stemness via the HIF-1α/glycolysis axis, making it a potential biomarker and therapeutic target in LUAD patients.

LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/ glycolysis axis in lung adenocarcinoma

Background Patients with triple-negative breast cancer (TNBC) face a major challenge of the poor prognosis, and N6-methyladenosine-(m6A) mediated regulation in cancer has been proposed. Therefore, this study aimed to explore the prognostic roles of m6A-related long non-coding RNAs (LncRNAs) in TNBC. Methods Clinical information and expression data of TNBC samples were collected from TCGA and GEO databases. Pearson correlation, univariate, and multivariate Cox regression analysis were employed to identify independent prognostic m6A-related LncRNAs to construct the prognostic score (PS) risk model. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PS risk model. A competing endogenous RNA (ceRNA) network was established for the functional analysis on targeted mRNAs. Results We identified 10 independent prognostic m6A-related LncRNAs (SAMD12-AS1, BVES-AS1, LINC00593, MIR205HG, LINC00571, ANKRD10-IT1, CIRBP-AS1, SUCLG2-AS1, BLACAT1, and HOXB-AS1) and established a PS risk model accordingly. Relevant results suggested that TNBC patients with lower PS had better overall survival status, and ROC curves proved that the PS model had better prognostic abilities with the AUC of 0.997 and 0.864 in TCGA and GSE76250 datasets, respectively. Recurrence and PS model status were defined as independent prognostic factors of TNBC. These ten LncRNAs were all differentially expressed in high-risk TNBC compared with controls. The ceRNA network revealed the regulatory axes for nine key LncRNAs, and mRNAs in the network were identified to function in pathways of cell communication, signaling transduction and cancer. Conclusion Our findings proposed a ten-m6A-related LncRNAs as potential biomarkers to predict the prognostic risk of TNBC.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/jcla.23779

A ten N6‐methyladenosine‐related long non‐coding RNAs signature predicts prognosis of triple‐negative breast cancer

ABSTRACT The current paper investigates how long non-coding RNA (lncRNA) FAM83A antisense RNA 1 (lncRNA FAM83A-AS1) affected the epithelial-mesenchymal transformation (EMT), growth, invasion and migration of lung adenocarcinoma (LUAD) via targeting miRNA-141-3p. The GEPIA and ENCORI databases were used to analyze differences in lncRNA FAM83A-AS1 levels within LUAD samples. FAM83A-AS1 and miR-141-3p levels were assessed using qRT-PCR among 30 LUAD samples and surrounding normal tissues. In addition, we analyzed how FAM83A-AS1 affected proliferation, invasion, migration, and EMT processes of LUAD cells by targeting miR-141-3p through EdU, CCK-8 assay, scratch assay, transwell migration and invasion assay, immunofluorescence (IF) staining and WB assay. MicroRNAs targeting FAM83A-AS1 were screened using AnnoLnc2 and identified by RT-qPCR. Dual-luciferase assays were utilized to evaluate the connection between FAM83A-AS1 and miR-141-3p. FAM83A-AS1 expression was remarkably raised in lung cancer cells and tissue samples; however, miR-141-3p level markedly reduced relative to healthy samples. FAM83A-AS1 silencing suppressed EMT, growth, invasion and migration of LUAD cells. MiR-141-3p was the possible FAM83A-AS1 binding target negatively associated with FAM83A-AS1. The miR-141-3p inhibitor partly abolished the FAM83A-AS1 knockdown-induced inhibition on EMT, cell growth, invasion and migration in LUAD cells. In addition, miR-141-3p down-regulation abolished the inhibition of E-box-bound zinc finger protein 1 and 2 protein production following FAM83A-AS1 knockdown. According to our results, FAM83A-AS1/miR-141-3p axis plays an important role in LUAD occurrence and development. FAM83A-AS1 sponged miR-141-3p to down-regulate the level of the latter within LUAD and thereby encouraging LUAD development and suggesting a possible novel therapeutic approach for LUAD. Graphical abstract

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2022.2037871?needAccess=true

Long non-coding RNA FAM83A antisense RNA 1 (lncRNA FAM83A-AS1) targets microRNA-141-3p to regulate lung adenocarcinoma cell proliferation, migration, invasion, and epithelial-mesenchymal transition progression

Background: Recent researches have pinpointed that long non-coding RNA (lncRNA) was tightly related to the carcinogenesis. However, the function of lncRNA in esophageal cell squamous carcinoma (ESCC) remains to be explored. In the current study, we assessed the expression pattern and the biological function of FAM83A-AS1 in ESCC. Methods: qRT-PCR was used to detect the expression of FAM83A-AS1, miR-214, and CDC25B expression in ESCC tissues and cell lines. CCK-8, transwell, apoptosis and cell cycle assays were performed to define the function of FAM83A-AS1 in ESCC cells. Furthermore, the regulation of miR-214 by FAM83A-AS1 was defined by qRT- PCR and rescue assays. In addition, the association between CDC25B, miR-214, CDC25B was confirmed by qRT-PCR. Results: Here, we discovered that FAM83A-AS1 was strongly expressed in ESCC tissues. FAM83A-AS1 abundance was associated with TNM stages and the differentiation grade of ESCC patients. The receiver operating characteristic curve (ROC) analysis indicated the high accuracy of FAM83A-AS1 in ESCC diagnosis. Functionally, inhibiting FAM83A-AS1 repressed cell proliferation, migration, and invasion in ESCC. In addition, we found that FAM83A-AS1 accelerated the cell cycle while inhibited cell apoptosis. Mechanistically, we found that FAM83A-AS1 regulated miR-214 expression, and there was a negative correlation between miR-214 and FAM83A-AS1 in ESCC. Rescue assay indicated that miR-214 could impair the suppressing effect of cell migration induced by FAM83A-AS1 depletion. Furthermore, CDC25B was a direct target of miR-214, and FAM83A-AS1 enhanced CDC25B expression while miR-214 positively CDC25B expression in ESCC. Conclusions: Collectively, we concluded that FAM83A-AS1 facilitated ESCC progression by regulating the miR-214/CDC25B axis. Our study showed FAM83A-AS1 may act as a promising target for ESCC diagnosis and therapy.

/pdf/lncrna-fam83a-as1-promotes-escc-progression-by-regulating-fmj07hdem9.pdf

LncRNA FAM83A-AS1 promotes ESCC progression by regulating miR-214/CDC25B axis.

Background Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy, which has posed a great challenge to public health, especially in China. Dysregulation of long non-coding RNAs is involved in the occurrence, development, invasion, and metastasis of multiple cancers including ESCC. However, little is known about the function of MIR205HG in ESCC.
 Methods
 We used qRT-PCR to detect the expression level of MIR205HG, miR-214, and SOX4 in human ESCC tissues and cell lines. Loss-of-functional assays were performed to test the impact of MIR205HG on cell proliferation, metastasis, and apoptosis process via CCK-8, transwell, and flow cell cytometry assays. Additionally, the downstream molecular mechanism of MIR205HG in ESCC was explored.
 Results
 Here, we found MIR205HG was substantially up-regulated in ESCC, and there was a positive correlation between MIR205HG expression and tumor size and lymphatic metastasis of ESCC patients. Inhibition of MIR205HG attenuated cell proliferation, migration, and invasion. Silencing MIR205HG increased G1 phase cell counts and decreased S phase cell counts, along with increased apoptotic cell populations. Notably, the rescue assays indicated that miR-214 could partly reverse the influence of MIR205HG on ESCC cell migration. We also found that SOX4 was a direct target mRNA of miR-214, and MIR205HG could act as a molecular sponge to regulate SOX4 expression in ESCC.
 Conclusion
 Taken together, our findings demonstrate that MIR205HG promotes ESCC progression by regulating the miR-214/SOX4 axis. MIR205HG may be a novel candidate target for ESCC diagnosis and therapy.

LncRNA MIR205HG Drives Esophageal Squamous Cell Carcinoma Progression by Regulating miR-214/SOX4 Axis

The tumor microenvironment (TME) is defined as a complex and dynamic tissue entity composed of endothelial, stromal, immune cells, and the blood system. The homeostasis and evolution of the TME are governed by intimate interactions among cellular compartments. The malignant behavior of cancer cells, such as infiltrating growth, proliferation, invasion, and metastasis, is predominantly dependent on the bidirectional communication between tumor cells and the TME. And such dialogue mainly involves the transfer of multifunctional regulatory molecules from tumor cells and/or stromal cells within the TME. Interestingly, increasing evidence has confirmed that exosomes carrying regulatory molecules, proteins, and nucleic acids act as an active link in cellular crosstalk in the TME. Notably, extensive studies have identified non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), that could be encapsulated by exosomes, which regulate the coordinated function within the TME and thus participate in cancer development and progression. In this review, we summarize recent literature around the topic of the functions and mechanisms of exosomal ncRNAs in the TME and highlight their clinical significance.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.900155/pdf

Crosstalk of Exosomal Non-Coding RNAs in The Tumor Microenvironment: Novel Frontiers

Accumulating evidence has revealed that m6A modification, the predominant RNA modification in eukaryotes, adds a novel layer of regulation to the gene expression. Dynamic and reversible m6A modification implements sophisticated and crucial functions in RNA metabolism, including generation, splicing, stability, and translation in messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). Furthermore, m6A modification plays a determining role in producing various m6A-labeling RNA outcomes, thereby affecting several functional processes, including tumorigenesis and progression. Herein, we highlighted current advances in m6A modification and the regulatory mechanisms underlying mRNAs and ncRNAs in distinct cancer stages. Meanwhile, we also focused on the therapeutic significance of m6A regulators in clinical cancer treatment.

Novel insights into m6A modification of coding and non-coding RNAs in tumor biology: From molecular mechanisms to therapeutic significance

Colorectal cancer (CRC) is a common malignancy with high mortality. However, the molecular mechanisms underlying CRC remain unclear. Controversies over the exact functions of non-coding RNAs (ncRNAs) in the progression of CRC have been prevailing for multiple years. Recently, accumulating evidence has demonstrated the regulatory roles of ncRNAs in various human cancers, including CRC. The intracellular signaling pathways by which ncRNAs act on tumor cells have been explored, and in CRC, various studies have identified numerous dysregulated ncRNAs that serve as oncogenes or tumor suppressors in the process of tumorigenesis through diverse mechanisms. In this review, we have summarized the functions and mechanisms of ncRNAs (mainly lncRNAs, miRNAs, and circRNAs) in the tumorigenesis of CRC. We also discuss the potential applications of ncRNAs as diagnostic and prognostic tools, as well as therapeutic targets in CRC. This review details strategies that trigger the recognition of CRC-related ncRNAs, as well as the methodologies and challenges of studying these molecules, and the forthcoming clinical applications of these findings.

/pdf/non-coding-rnas-in-colorectal-cancer-their-functions-and-2mixwtmw.pdf

Zimo Jia

Papers

LncRNA FAM83A-AS1 promotes ESCC progression by regulating miR-214/CDC25B axis.

LncRNA MIR205HG Drives Esophageal Squamous Cell Carcinoma Progression by Regulating miR-214/SOX4 Axis

Crosstalk of Exosomal Non-Coding RNAs in The Tumor Microenvironment: Novel Frontiers

Novel insights into m6A modification of coding and non-coding RNAs in tumor biology: From molecular mechanisms to therapeutic significance

Non-Coding RNAs in Colorectal Cancer: Their Functions and Mechanisms