• Circular RNA
• HOTAIR-miR-34a-5p
• Hepatocellular carcinoma
• Long non-coding RNA
• Metastasis
• MicroRNA

• Humans
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/genetics
• Liver Neoplasms/secondary
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Metastasis
• Gene Expression Regulation, Neoplastic
• Epithelial-Mesenchymal Transition

• Colon cancer
• Digestive system cancers
• Long non-coding RNAs
• Small nucleolar RNA host gene 16

• BET inhibitor (BETi)
• Cell division cycle 25B (CDC25B)
• gemcitabine
• gemcitabine-resistant (gemR) models
• pancreatic ductal adenocarcinoma (PDAC)
• patient-derived xenograft (PDX) models

• biomarker
• cancer immunotherapy
• cell division cycle 25B
• hepatocellular carcinoma
• immune activation

• delivery systems
• drug resistance
• hepatocellular carcinoma
• microRNAs
• targeted therapy
• tumor heterogeneity

• Humans
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/genetics
• Liver Neoplasms/therapy
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Gene Expression Regulation, Neoplastic
• Animals
• Biomarkers, Tumor/genetics

• Biomarkers
• Diagnostic
• Hepatocellular carcinoma
• Long noncoding Ribonucleic acid
• Messenger Ribonucleic acid
• Micro Ribonucleic acid
• Prognostic

• HMGA2
• cancer
• epithelial-mesenchymal transition
• extracellular matrix
• gene therapy

• dysregulated
• gene targets
• hepatitis B-associated carcinoma (HBV-HCC)
• microRNA (miRNA)
• modulate
• pathways

• Humans
• Carcinoma, Hepatocellular/genetics
• Liver Neoplasms/genetics
• South Africa/epidemiology
• Hepatitis B/complications
• Hepatitis B/genetics
• MicroRNAs/genetics

• HHSN261200800001C NCI NIH HHS
• HHSN261200800001E NCI NIH HHS

• CDC25B
• DNA damage
• E2F3
• Mitoxantrone
• Stomach adenocarcinoma

• Humans
• Mitoxantrone/pharmacology
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Adenocarcinoma/drug therapy
• Adenocarcinoma/genetics
• DNA Damage
• Mitosis
• Luciferases
• E2F3 Transcription Factor
• cdc25 Phosphatases/genetics

• 2022KY459 Health Science and Technology Program of Zhejiang Province
• 2022KY459 Health Science and Technology Program of Zhejiang Province
• 2022KY459 Health Science and Technology Program of Zhejiang Province
• 2022KY459 Health Science and Technology Program of Zhejiang Province
• 2022KY459 Health Science and Technology Program of Zhejiang Province
• 2022KY459 Health Science and Technology Program of Zhejiang Province

• CD8(+)T cells
• Hepatocellular carcinoma
• IQGAP1
• Immune escape
• M2 macrophages
• MISP
• PD-L1
• STAT3

• 81930078 National Natural Science Foundation of China (National Science Foundation of China)
• 81872246 National Natural Science Foundation of China (National Science Foundation of China)
• 81902838 National Natural Science Foundation of China (National Science Foundation of China)
• 7204284 Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)

• Cancer
• HMGA2
• circRNAs
• lncRNA
• miRNA

• TMX resistant
• bioinformatics
• breast cancer
• ceRNA
• lncRNA
• prognostic

• Biomarkers
• DNA methylation
• Epidrugs
• Epigenetics
• Hepatocellular carcinoma
• Histone modification
• ncRNAs

Hepatocellular carcinoma (HCC) is a common malignancy in the world, with high mortality and poor prognosis. Hepatitis B virus (HBV) is one of the key factors implicated in the occurrence of HCC. Increasing evidence suggests that miRNAs play important roles in the development and metastasis of HBV-associated HCC (HBV-HCC). Here, we performed CCK8 (Cell count kit-8), EdU (5-ethynyl-2’-deoxyuridine) incorporation assay, wound-healing assay, transwell assay to study the changes in the cellular phenotype. Luciferase reporter assay, RNA pull-down experiment, RT-qPCR and western blotting were employed to study molecular mechanism. In addition, we also constructed a mouse HCC xenograft model to verify the functional role of HMMR-AS1/miR-627-3p/HMGA2 signal axis in vivo. Our study demonstrated that HMMR-AS1 was highly expressed in HCC tissues and cell lines, suggesting its implication in the progression of HCC. In addition, in vitro experiments showed that high HMMR-AS1 expression facilitated the migration, invasion, and proliferation of HCC cells. We further revealed that HMMR-AS1 promoted the malignant phenotype of HCC cells by regulating miR-627-3p/HMGA2 axis. Together, our data suggest that HMMR-AS1 regulates HBV-HCC progression via miR-627-3p/HMGA2 axis.

• HBV-HCC
• HMGA2
• HMMR-AS1
• miR-627-3p

Trametes robiniophila (Huaier) is available to refrain lung cancer (LC) cell progression, but its impact and mechanism on angiogenesis of LC are not proved. The study was to explore the potential mechanism of Huaier repressing angiogenesis and tumor growth in LC via strengthening let-7d-5p and targeting NAP1L1. Let-7d-5p and NAP1L1 expression was detected in LC tissues and cells (A549). Pretreatment of A549 cells was with Huaier. Transfection of changed let-7d-5p and NAP1L1 was to A549 cells to uncover their roles in LC cell progression with angiogenesis. Evaluation of the impact of let-7d-5p on angiogenesis in LC was in vitro in a mouse xenograft model. Identification of the targeting of let-7d-5p with NAP1L1 was clarified. The results clarified reduced let-7d-5p but elevated NAP1L1 were manifested in LC. Huaier restrained angiogenesis and tumor growth of LC in vivo and in vitro; Augmented let-7d-5p or declined NAP1L1 motivated the therapy of Huaier on LC; Let-7d-5p negatively modulated NAP1L1; Elevated NAP1L1 reversed the influence of enhancive let-7d-5p. These results strongly suggest that Huaier represses angiogenesis and tumor growth in LC via strengthening let-7d-5p and targeting NAP1L1. Huaier/let-7d-5p/NAP1L1 axis is supposed to be a promising target for the treatment of angiogenesis and tumor growth in LC via elevated let-7d-5p and targeted NAP1L1.

• Angiogenesis
• Let-7d-5p
• Lung cancer
• NAP1L1
• Trametes robiniophila

Being located on 17q25.1, small nucleolar RNA host gene 6 (SNHG16) is a member of SNHG family of long non-coding RNAs (lncRNA) with 4 exons and 13 splice variants. This lncRNA serves as a sponge for a variety of miRNAs, namely miR-520a-3p, miR-4500, miR-146a miR-16–5p, miR-98, let-7a-5p, hsa-miR-93, miR-17-5p, miR-186, miR-302a-3p, miR-605-3p, miR-140-5p, miR-195, let-7b-5p, miR-16, miR-340, miR-1301, miR-205, miR-488, miR-1285-3p, miR-146a-5p, and miR-124-3p. This lncRNA can affect activity of TGF-β1/SMAD5, mTOR, NF-κB, Wnt, RAS/RAF/MEK/ERK and PI3K/AKT pathways. Almost all studies have reported oncogenic effect of SNHG16 in diverse cell types. Here, we explain the results of studies about the oncogenic role of SNHG16 according to three distinct sets of evidence, i.e., in vitro, animal, and clinical evidence.

• SNHG6
• biomarker
• cancer
• expression
• lncRNA

The emergence and recurrence of ovarian cancer are associated with ovarian cancer stem cells. For cancer treatment, gene delivery of microbubbles (MB)-mediated microRNA (miRNA) is considered as a promising approach. In this study, our aim is to investigate the effects of MB-mediated let-7b-5p inhibitor on the proliferation and stemness characteristics of ovarian cancer (OVCA) cells. Let-7b-5p inhibitor mediated by MB was prepared (termed MB-let-7b-5p inhibitor), and the effects of MB-let-7b-5p inhibitor and let-7b-5p inhibitor on OVCA cell viability, proliferation and stemness characteristics were investigated. We found that MB-let-7b-5p inhibitor presented a higher transfection efficiency than let-7b-5p inhibitor alone. The inhibitory effect of MB-let-7b-5p inhibitor on OVCA cells was more significant than let-7b-5p inhibitor. Let-7b-5p targeted DEAD (Asp-Glu-Ala-Asp)-box helicase 19A (DDX19A), which was downregulated in OVCA cells. The downregulation of DDX19A reversed the inhibitory effects of MB-let-7b-5p inhibitor on OVCA cells. To sum up, we found that MB-let-7b-5p suppressed OVCA cell malignant behaviors by targeting DDX19A.

• OVCA
• ddx19a
• let-7b-5p
• mb
• stemness characteristics

• Homeobox A1
• atherosclerosis
• let-7b-5p
• oxidized low-density lipoprotein
• regulator of reprogramming

Parkinson's disease (PD), a common multifactorial neurodegenerative disease, is characterized by irreversible loss of dopaminergic neurons in the substantia nigra. In-depth study of the pathogenesis of PD is of great importance. High-mobility group AT-hook 2 (HMGA2) has been proposed to be implicated with neuronal differentiation and impairment of cognitive function. However, whether HMGA2 plays a role in PD is rarely explored. In the present study, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD mice models and N-methyl-4- phenylpyridinium (MPP⁺)-treated SH-SY5Y cell models were established. Reverse transcription-quantitative PCR showed that HMGA2 displayed low levels in brain tissues of MPTP-treated mice and MPP⁺-treated SH-SY5Y cells. Moreover, HMGA2 overexpression suppressed SH-SY5Y cell apoptosis. Additionally, let-7b-5p bound with HMGA2 3′ untranslated region (UTR), and its expression was negatively correlated with HMGA2 level. Moreover, let-7b-5p presented high levels in brain tissues of PD mice and MPP⁺-treated SH-SY5Y cells, and knockdown of let-7b-5p inhibited SH-SY5Y cell apoptosis. Rescue assays illustrated that HMGA2 neutralized the promotive effects of let-7b-5p mimics on SH-SY5Y cell apoptosis. In conclusion, the present study demonstrated that let-7b-5p contributes to cell apoptosis in PD by targeting HMGA2, which offers a potential theoretical basis for the study of effective therapy in PD.

• Parkinson's disease
• cell apoptosis
• high‑mobility group AT‑hook 2
• let‑7b‑5p

The BCR-ABL fusion gene plays a crucial role in the leukemogenesis of chronic myeloid leukemia (CML). The BCR-ABL oncoprotein encoded by this fusion gene has been extensively studied. However, research on whether BCR-ABL also affects circular RNAs (circRNAs) is limited. This study aimed to explore the new fusion circRNAs produced by BCR-ABL and their role in CML cells. In this study, we identified a novel fusion circRNA, named F-circBA1, originating from BCR-ABL in K562 and K562/G01 cells using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Sanger sequencing. qRT-PCR of the nuclear RNA and cytoplasmic RNA were separated, indicating that F-circBA1 was mainly localized in the cytoplasm. Cell counting kit-8 assay and flow cytometry showed that F-circBA1 knockdown by shRNA prevented the proliferation of K562 and K562/G01 cells, and the cell cycle was arrested at G2/M. Mechanically, dual-luciferase reporter assay and western blotting assay showed that F-circBA1 sponged miR-148-3p and F-circBA1 silencing decreased CDC25B expression in vitro. Furthermore, the results of the murine leukemogenesis model showed that F-circBA1 knockdown suppressed leukemogenesis in vivo. Besides, we found the existence of F-circBA1 in some patients with BCR-ABL-positive CML. In conclusion, these results demonstrate the presence of F-circBA1 and its oncogenic role in CML cells.

• bcr-abl
• chronic myeloid leukemia
• fusion circRNAs
• proliferation

• Cancer stem cells
• Cisplatin resistance
• Hsa-miR-139-5p
• Ovarian cancer
• SDC4
• lncRNA WDFY3-AS2

• YWJKJJHKYJJ-B183069 Beijing Medical and Health Public Welfare Foundation Medical Science Research Fund Project

• EMT
• cancer
• long non-coding RNAs
• small nucleolar RNA host genes

• Autophagy
• Gefitinib resistance
• HCC827GR cells
• Lung cancer
• lncRNA MITA1

• Cancer
• Cell cycle
• Cell cycle-directed anti-cancer therapies
• HMGA
• TP53

• Cell Cycle Checkpoints/physiology
• DNA Damage
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Genomic Instability
• HMGA Proteins/genetics
• HMGA Proteins/metabolism
• Humans
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/pathology
• Signal Transduction
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/metabolism

High‐mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma (HCC) cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in HCC cells remains largely unclear. Here, we showed that the expression HMGA2 was upregulated in HCC, and that elevated HMGA2 could promote tumor metastasis. Incubation of HCC cells with epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through the PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF‐induced HMGA2 expression and histone H3‐K9 acetylation, whereas a phosphorylation‐mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3‐K9 acetylation in HCC cells. Furthermore, we identified that p300‐mediated H3‐K9 acetylation participates in EGF‐induced HMGA2 expression in HCC. In addition, the levels of H3‐K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.

• EGFR
• HMGA2
• hepatocellular carcinoma
• histone H3
• p300

Non-coding RNAs such as microRNAs, long non-coding RNAs, and circular RNAs contribute to the development and progression of hepatocellular carcinoma through epigenetic association. Long non-coding RNAs and circular RNAs act as competing endogenous RNAs that contain binding sites for miRNAs and thus compete with the miRNAs, which results in promotion of miRNA target gene expression, thereby leading to proliferation and metastasis of hepatocellular carcinoma. Competing endogenous RNAs have the potential to become diagnostic biomarkers and therapeutic targets for treatment of hepatocellular carcinoma.

The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes in HCC, including cancer cell growth, epithelial to mesenchymal transition (EMT), metastasis, and chemoresistance. In this review, we summarize recent discoveries, which are specific ceRNA regulatory networks (lncRNA/circRNA-miRNA-mRNA) in HCC and discuss their clinical significance.

• circular RNA
• competing endogenous RNA
• hepatocellular carcinoma
• long non-coding RNA
• microRNA

• Biomarker
• Human cancer
• Long non-coding RNA
• Mechanism
• SNHG16

• Natural Science Foundation of Hunan Province
• National Natural Science Foundation of China
• Changsha Science and Technology Board

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncoding RNAs (ncRNAs) that occupy over 90% of the human genome, and their main function is to directly or indirectly regulate messenger RNA (mRNA) expression and participate in the tumorigenesis and progression of malignances. In particular, some lncRNAs can interact with miRNAs as competing endogenous RNAs (ceRNAs) to modulate mRNA expression. Accordingly, these RNA molecules are interrelated and coordinate to form a dynamic lncRNA-mediated ceRNA regulatory network. Mounting evidence has revealed that lncRNAs that act as ceRNAs are closely related to tumorigenesis. To date, numerous studies have established many different regulatory networks in hepatocellular carcinoma (HCC), and perturbations in these ceRNA interactions may result in the initiation and progression of HCC. Herein, we emphasize recent advances concerning the biological function of lncRNAs as ceRNAs in HCC, with the aim of elucidating the molecular mechanism underlying these HCC-related RNA molecules and providing novel insights into the diagnosis and treatment of HCC.

• Hepatocellular carcinoma
• Long noncoding RNA
• MicroRNA
• Competing endogenous RNA
• Function
• Mechanism

• Carcinoma, Hepatocellular/genetics
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• Liver Neoplasms/genetics
• MicroRNAs
• RNA, Long Noncoding/genetics

• SPACA6P-AS
• cancer
• ceRNET
• miR-125a
• non-coding RNA

• Carcinoma, Hepatocellular/genetics
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• Liver Neoplasms/genetics
• MicroRNAs/genetics
• RNA, Long Noncoding/genetics
• RNA, Messenger/genetics

Long non‐coding RNAs (lncRNAs) widely participate in ESCC development and progression; however, the prognostic factors and therapeutic strategies implicated in ESCC development and progression remain to be under investigation. The purpose of the current study was to explore whether WDFY3‐AS2 may be a potential prognostic factor and investigate its biological functions in ESCC. Here, WDFY3‐AS2 was frequently down‐regulated in ESCC tissues and cells, and its expression was correlated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Moreover, WDFY3‐AS2 down‐regulation significantly promoted cell proliferation and invasion, whereas WDFY3‐AS2 up‐regulation markedly suppressed cell proliferation and invasion in ESCC EC9706 and TE1 cells, coupled with EMT phenotype alterations. WDFY3‐AS2 functioned as a competing endogenous RNA (ceRNA) for sponging miR‐2355‐5p, further resulted in the up‐regulation of its target gene SOCS2, followed by suppression of JAK2/Stat5 signalling pathway, to suppress ESCC cell proliferation and invasion in EC9706 and TE1 cells. These findings suggest that WDFY3‐AS2 may participate in ESCC development and progression, and may be a novel prognostic factor for ESCC patients, and thus targeting WDFY3‐AS2/miR‐2355‐5p/SOCS2 signalling axis may be a novel therapeutic strategy for ESCC patients.

• WDFY3-AS2
• ceRNA mechanism
• invasion and metastasis
• microRNA-2355-5p
• oesophageal squamous cell carcinoma
• suppressors of cytokine signalling 2

Long noncoding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) has been revealed to be involved in the tumorigenesis of neuroblastoma. However, the role of SNHG16 in regulating cisplatin sensitivity in neuroblastoma remains largely unknown.

The expression of SNHG16, microRNA (miR)-338-3p and polo-like kinase 4 (PLK4) mRNA was measured using quantitative real-time polymerase chain reaction. The protein levels of PLK4, multidrug resistance protein 1 (MRP1), multidrug-resistance gene 1-type p-glycoprotein (P-gp) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins were detected by Western blot. The half maximal inhibitory concentration (IC50) value, cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 assays or Transwell assay. Apoptotic cells were measured by Flow cytometry. The interaction between miR-338-3p and SNHG16 or PLK4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay. In vivo experiments were conducted through the murine xenograft model.

SNHG16 was up-regulated, while miR-338-3p was down-regulated in cisplatin-resistant neuroblastoma tissues and cells. SNHG16 silencing weakened cisplatin resistance, reflected by the reduction of IC50 value, down-regulation of MRP-1 and P-gp protein expression, suppression of proliferation, migration and invasion, as well as enhancement of apoptosis in SNHG16 deletion cisplatin-resistant neuroblastoma cells. Besides that, SNHG16 could regulate PLK4 expression by sponging miR-338-3p and SNHG16/miR-338-3p/PLK4 axis could affect the activation of PI3K/AKT pathway in cisplatin-resistant neuroblastoma cells. MiR-338-3p inhibition attenuated SNHG16 deletion-mediated impairment on cisplatin resistance and PLK4 overexpression reversed the decrease of cisplatin-resistance induced by miR-338-3p re-expression. Furthermore, SNHG16 knockdown contributed to the anti-tumor effect of cisplatin in neuroblastoma in vivo.

SNHG16 contributed to the tumorigenesis and cisplatin resistance in neuroblastoma possibly through miR-338-3p/PLK4 pathway, indicating a novel insight for overcoming chemoresistance in neuroblastoma patients.

• Cisplatin resistance
• Neuroblastoma
• PLK4
• SNHG16
• miR-338-3p

• Biogenesis of secondary tumor
• Gene expression regulation
• Hepatocellular carcinoma
• Protein synthesis
• Tumor microenvironment
• RNA binding proteins