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Background: Many studies have shown that circular RNAs (circRNAs) are abnormally expressed in various tumor tissues and served as a key regulator in the occurrence and development of cancer. However, in hepatocellular carcinoma (HCC), the molecular mechanism of circRNAs in body fluids remains to be further explored. Methods: The expression levels of genes and proteins were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting, respectively. Cell counting Kit‐8 (CCK‐8), 5‐Ethynyl‐2'‐deoxyuridine (EdU), wound healing assay, Transwell assays, flow cytometry, and tumor formation models in nude mice were conducted to investigate the effects of circFAM114A2 on HCC cells both in vitro and in vivo. RNA antisense purification (RAP), dual luciferase reporter assays and rescue assays were carried out to verify the interaction between circFAM114A2, miR‐630 and HHIP. Results: CircFAM114A2 was significantly downregulated in HCC tissues and was associated with microvascular invasion and lymph node metastasis of HCC patients. We also observed that circFAM114A2 was lowly expressed in HCC plasma, which may serve as an effective biomarker to screen HCC patients from healthy controls (area under curve (AUC)=0.922). In vitro, circFAM114A2 overexpression significantly blunted HCC cell proliferation, migration, invasion, and promoted apoptosis, whereas circFAM114A2 silencing posed opposite effects. In vivo, circFAM114A2 overexpression inhibited the growth of HCC cells. Mechanistically, circFAM114A2 could increase the expression of the tumor suppressor HHIP via acting as a sponge for miR‐630. Conclusions: CircFAM114A2 exerts a tumor suppressor role in HCC through miR‐630/HHIP axis, and may be served as a potential diagnostic and therapeutic biomarker for HCC patients. [ABSTRACT FROM AUTHOR]

Smoking is one of the major environmental risk factors for lung cancer. In recent years, the role of long-chain noncoding RNAs (lncRNAs) in chemical carcinogenesis has attracted extensive research attention. In this study, we treated human bronchial epithelial cells with cigarette smoke extract (CSE) at a dose of 2 μg/ml to establish a malignantly transformed cellular model (16HBE-M). Screening of lncRNAs highly expressed in transformed cells via differential analysis revealed a crucial role of linc00152 in CSE-induced malignant transformation. The linc00152 serum level in CSE-exposed individuals was increased in a dose-dependent manner and its high expression associated with metastasis and proliferation of lung cancer tissue. In malignantly transformed 16HBE-M cells, linc00152 was involved in regulation of cell adhesion, epithelial transition and other malignant phenotypes, which in turn, affected in vivo metastasis. Interference with linc00152 expression led to G1/S arrest and inhibition of proliferation of 16HBE-M and H1299 cells. Furthermore, linc00152 promoted cyclin D1 expression and G1/S transition by functioning as an endogenous competitive RNA targeting miR-193b. Our collective findings supported a critical regulatory role of linc00152 in cell cycle alterations and abnormal proliferation in CSE-induced malignant transformation of human bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

Lead is a heavy metal pollutant that is widely present in the environment and can seriously harm human health, especially the nervous system. Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes; however, there remains a lack of in-depth studies on the molecular mechanisms associated with lead neurotoxicity. Here, our results showed that lead exposure inhibited cell proliferation and promoted cell apoptosis. We observed that lncRNAL20992 was significantly upregulated in a lead-induced neuronal-injury cell model according to quantitative reverse transcription polymerase chain reaction. Silencing lncRNAL20992 revealed its significant functions involved in promoting cell apoptosis and inhibiting cell proliferation according to cell-counting kit-8, EdU assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and western blot. To elucidate the molecular mechanisms of lncRNAL20992, we used RNA pulldown mass spectrometry combined with bioinformatics analysis to discover 4 proteins (AIFM1, HSP7C, GRP78, and LMNA) that interacted with lncRNAL20992. Western blot analysis indicated that lncRNAL20992 involved in lead-induced neuronal injury was mediated by the 4 proteins. Our study constitutes the first investigation of the functions and related mechanisms of lncRNAL20992 and offered valuable insight into understanding the roles of lncRNA in lead-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

circNOL10 is a circular RNA expressed at low levels in lung cancer, though its functions in lung cancer remain unknown. Here, the function and molecular mechanism of circNOL10 in lung cancer development are investigated using in vitro and in vivo studies, and it is shown that circNOL10 significantly inhibits the development of lung cancer and that circNOL10 expression is co‐regulated by methylation of its parental gene Pre‐NOL10 and by splicing factor epithelial splicing regulatory protein 1 (ESRP1). circNOL10 promotes the expression of transcription factor sex comb on midleg‐like 1 (SCML1) by inhibiting transcription factor ubiquitination and thus also affects regulation of the humanin (HN) polypeptide family by SCML1. circNOL10 also affects mitochondrial function through regulating the humanin polypeptide family and affecting multiple signaling pathways, ultimately inhibiting cell proliferation and cell cycle progression, and promoting the apoptosis of lung cancer cells, thereby inhibiting lung cancer development. This study investigates the functions and molecular mechanisms of circNOL10 in the development of lung cancer and reveals its involvement in the transcriptional regulation of the HN polypeptide family by SCML1. The results also demonstrate the inhibitory effect of HN on lung cancer cells growth. These findings may identify novel targets for the molecular therapy of lung cancer. This study provides new evidence for the molecular mechanism whereby circRNAs may affect transcriptional regulation in lung cancer cells, and also reveals that circNOL10 inhibits lung cancer development by promoting SCLM1‐mediated transcriptional regulation of the humanin (HN) polypeptide family. The results also demonstrate the inhibitory effect of HN on lung cancer growth. [ABSTRACT FROM AUTHOR]

Smoking is one of the major environmental risk factors for lung cancer. In recent years, the role of long-chain noncoding RNAs (lncRNAs) in chemical carcinogenesis has attracted extensive research attention. In this study, we treated human bronchial epithelial cells with cigarette smoke extract (CSE) at a dose of 2 μg/ml to establish a malignantly transformed cellular model (16HBE-M). Screening of lncRNAs highly expressed in transformed cells via differential analysis revealed a crucial role of linc00152 in CSE-induced malignant transformation. The linc00152 serum level in CSE-exposed individuals was increased in a dose-dependent manner and its high expression associated with metastasis and proliferation of lung cancer tissue. In malignantly transformed 16HBE-M cells, linc00152 was involved in regulation of cell adhesion, epithelial transition and other malignant phenotypes, which in turn, affected in vivo metastasis. Interference with linc00152 expression led to G1/S arrest and inhibition of proliferation of 16HBE-M and H1299 cells. Furthermore, linc00152 promoted cyclin D1 expression and G1/S transition by functioning as an endogenous competitive RNA targeting miR-193b. Our collective findings supported a critical regulatory role of linc00152 in cell cycle alterations and abnormal proliferation in CSE-induced malignant transformation of human bronchial epithelial cells.

As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury.