The Role of PTEN in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.

CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells.

BACKGROUND: The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentiation, and polarization. However, the effects of mechanical force on circRNAs and the role of circRNAs in the mechanobiology of differentiation and remodeling in stretched periodontal ligament stem cells (PDLSCs) remain unclear. This article aims to explore the osteogenic function of mechanically sensitive circular RNA protein kinase D3 (circPRKD3) and elucidate its underlying mechanotransduction mechanism. MATERIALS AND METHODS: PDLSCs were elongated with 8% stretch at 0.5 Hz for 24 h using the Flexcell® FX-6000™ Tension System. CircPRKD3 was knockdown or overexpressed with lentiviral constructs or plasmids. The downstream molecules of circPRKD3 were predicted by bioinformatics analysis. The osteogenic effect of related molecules was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. RESULTS: Mechanical force enhanced the osteogenesis of PDLSCs and increased the expression of circPRKD3. Knockdown of circPRKD3 hindered PDLSCs from osteogenesis under mechanical force, while overexpression of circPRKD3 promoted the early osteogenesis process of PDLSCs. With bioinformatics analysis and multiple software predictions, we identified hsa-miR-6783-3p could act as the sponge of circPRKD3 to indirectly regulate osteogenic differentiation of mechanically stimulated PDLSCs. CONCLUSIONS: Our results first suggested that both circPRKD3 and hsa-miR-6783-3p could enhance osteogenesis of stretched PDLSCs. Furthermore, hsa-miR-6783-3p could sponge circPRKD3 to indirectly regulate RUNX2 during the periodontal tissue remodeling process in orthodontic treatment.

[Research Progress in the Regulatory Role of circRNA-miRNA Network in Bone Remodeling]. / circRNA-miRNAç½‘ç»œè°ƒæŽ§éª¨é‡å¡‘çš„ç ”ç©¶è¿›å±•.

The dynamic balance between bone formation and bone resorption is a critical process of bone remodeling. The imbalance of bone formation and bone resorption is closely associated with the occurrence and development of various bone-related diseases. Under both physiological and pathological conditions, non-coding RNAs (ncRNAs) play a crucial regulatory role in protein expression through either inhibiting mRNAs translation or promoting mRNAs degradation. Circular RNAs (circRNAs) are a type of non-linear ncRNAs that can resist the degradation of RNA exonucleases. There is accumulating evidence suggesting that circRNAs and microRNAs (miRNAs) serve as critical regulators of bone remodeling through their direct or indirect regulation of the expression of osteogenesis-related genes. Additionally, recent studies have revealed the involvement of the circRNAs-miRNAs regulatory network in the process by which mesenchymal stem cells (MSCs) differentiate towards the osteoblasts (OB) lineage and the process by which bone marrow-derived macrophages (BMDM) differentiate towards osteoclasts (OC). The circRNA-miRNA network plays an important regulatory role in the osteoblastic-osteoclastic balance of bone remodeling. Therefore, a thorough understanding of the circRNA-miRNA regulatory mechanisms will contribute to a better understanding of the regulatory mechanisms of the balance between osteoblastic and osteoclastic activities in the process of bone remodeling and the diagnosis and treatment of related diseases. Herein, we reviewed the functions of circRNA and microRNA. We also reviewed their roles in and the mechanisms of the circRNA-miRNA regulatory network in the process of bone remodeling. This review provides references and ideas for further research on the regulation of bone remodeling and the prevention and treatment of bone-related diseases.

The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets.

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.

Circular RNAs as biomarkers and therapeutic targets for gastrointestinal cancers.

Circular RNAs are a class of noncoding RNAs with covalently linked 5' and 3' ends that arise from backsplicing events. The absence of a 5' cap and a 3' poly(A) tail makes circular RNAs relatively more stable than their linear counterparts. They are evolutionary conserved and tissue-specific, and some show disease-specific expression patterns. Although their biological functions remain largely unknown, circular RNAs have been shown to play regulatory roles by acting as microRNA sponges, regulators of RNA-binding proteins, alternative splicing, and parental gene expression, and they could even encode proteins. Over the past few decades, circular RNAs have attracted wide attention in oncology owing to their implications in various tumors. Many circular RNAs have been characterized as key players in gastrointestinal cancers and influence cancer growth, progression, metastasis, and therapeutic resistance. Accumulating evidence reveals that their unique characteristics, coupled with their critical roles in tumorigenesis, make circular RNAs promising non-invasive clinical biomarkers for gastrointestinal cancers. In the present review, we summarized the biological roles of the emerging circular RNAs and their potential as biomarkers and therapeutic targets, which may help better understand their clinical significance in the management of gastrointestinal cancers.

Hsa_circ_0001326 inhibited the proliferation, migration, and invasion of trophoblast cells via miR-145-5p/TGFB2 axis.

PROBLEM: Preeclampsia (PE) is an obstetric disease involving multiple systems, which account for maternal and fetal complications and increased mortality. Circular RNAs (circRNAs) were recently deemed to associate with the pathogenesis of PE. This study aims to clarify the correlation between circRNA hsa_circ_0001326 and PE and explore its biological function in PE. METHOD OF STUDY: The expression of hsa_circ_0001326 in PE placentas was detected by real-time quantitative PCR (qRT-PCR). After overexpressing or inhibiting hsa_circ_0001326 in trophoblast cells, the cell growth, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assays. Western blot assay was applied to detect the epithelial-mesenchymal transition (EMT) proteins, E-cadherin and Vimentin. Furthermore, a dual-luciferase reporter assay was applied to verify the binding sites of hsa_circ_0001326, miR-145-5p, and transforming growth factor beta 2 (TGFB2). RESULTS: Hsa_circ_0001326 was found to be higher expressed in PE placentas than in normal placentas. Furthermore, hsa_circ_0001326 played a negative regulating role in trophoblast cell viability, migration, and invasion. Overexpression of hsa_circ_0001326 inhibited the viability, migration, and invasion of trophoblast cells, while inhibition of hsa_circ_0001326 showed opposite effects. Mechanistically, hsa_circ_0001326 sponged miR-145-5p to elevate TGFB2 expression in trophoblast cells. CONCLUSION: This study provided evidence that the up-regulated hsa_circ_0001326 in PE restrained trophoblast cells proliferation, migration, and invasion by sponging miR-145-5p to elevate TGFB2 expression. Our results might provide a novel insight into the role of hsa_circ_0001326 in the pathogenesis of PE.

Circ_FURIN knockdown assuages Testosterone-induced human ovarian granulosa-like tumor cell disorders by sponging miR-423-5p to reduce MTM1 expression in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. Thus, the study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism. METHODS: PCOS cell model was established by treating human ovarian granulosa-like tumor cells (KGN) with Testosterone (TTR). RNA expressions of circ_FURIN, microRNA-423-5p (miR-423-5p) and myotubularin 1 (MTM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was checked by Western blot. Cell proliferation was investigated by a 5-Ethynyl-29-deoxyuridine assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis for cell cycle. Apoptotic cells were quantified by flow cytometry analysis for cell apoptosis. The interplay between miR-423-5p and circ_FURIN or MTM1 was identified by dual-luciferase reporter and RNA pull-down assays. RESULTS: Circ_FURIN and MTM1 expressions were significantly upregulated, whereas miR-423-5p was downregulated in the ovarian cortex tissues of PCOS patients and TTR-treated KGN cells compared with controls. Circ_FURIN depletion relieved TTR-induced proliferation inhibition and apoptosis promotion. Besides, knockdown of miR-423-5p, a target miRNA of circ_FURIN, rescued circ_FURIN knockdown-mediated effects under TTR treatment. MiR-423-5p remitted TTR-induced cell disorders by binding to MTM1. Moreover, circ_FURIN modulated MTM1 expression through miR-423-5p. CONCLUSION: Circ_FURIN silencing protected against TTR-induced dysfunction by the miR-423-5p/MTM1 pathway in human ovarian granulosa-like tumor cells.

TGF-ß2-induced circ-PRDM5 regulates migration, invasion, and EMT through the miR-92b-3p/COL1A2 pathway in human lens epithelial cells.

CircRNA circ-PRDM5 (PR/SET domain 5) (circ-PRDM5) is overexpressed in age-related cataracts. Nevertheless, the biological role of circ-PRDM5 in posterior capsule opacities (PCO) (a common complication after cataract surgery) is unclear. Human lens epithelial cells SRA01/04 (LECs) were stimulated with TGF-ß2 (transforming growth factor beta-2) to mimic the PCO model in vitro. Cell viability, migration, and invasion were determined by MTT, transwell, or wound-healing assays. Protein levels of EMT (epithelial-to-mesenchymal transition) markers and COL1A2 (collagen type I alpha 2 chain) were analyzed by western blotting (WB). Relative expression of circ-PRDM5, miR-92b-3p, and COL1A2 mRNA was analyzed by qRT-PCR. The targeting relationship was confirmed by dual-luciferase reporter and RIP assays. We observed that circ-PRDM5 and COL1A2 were upregulated in PCO tissues and TGF-ß2-treated LECs, while miR-92b-3p was downregulated. Both circ-PRDM5 and COL1A2 knockdown impaired TGF-ß2-induced LEC migration, invasion, and EMT. Also, circ-PRDM5 could adsorb miR-92b-3p to regulate COL1A2 expression. Furthermore, miR-92b-3p inhibitor offset circ-PRDM5 knockdown-mediated influence on migration, invasion, and EMT of LECs under TGF-ß2 stimulation. Also, COL1A2 overexpression overturned the repressive influence of miR-92b-3p mimic on TGF-ß2-induced LEC migration, invasion, and EMT. In summary, TGF-ß2-induced circ-PRDM5 facilitated LEC migration, invasion, and EMT by adsorbing miR-92b-3p and increasing COL1A2 expression, offering new insights into the development of PCO.

Estrogen receptor ß2 (ERß2)-mediated upregulation of hsa_circ_0000732 promotes tumor progression via sponging microRNA-1184 in triple-negative breast cancer (TNBC).

BACKGROUND: The role of estrogen receptor ß (ERß) in the pathogenesis and development of breast cancer (BC) is controversial, and it is currently considered to play contradictory roles in different phenotypes. ERß2 is thought to promote the BC process, but its role in triple-negative breast cancer (TNBC) has not been reported. METHODS: In this study, we collected tumor tissues from 15 patients with TNBC and obtained a variety of TNBC cell lines as research objects. The plasmid vectors and RNA interference techniques were used to change the level of target genes in cells, quantitative PCR and Western Blots were used to detect gene expression levels, CCK-8 and EdU assay were used to detect cell growth, and Transwell was used to detect cell migration and invasion. Dual-luciferase gene reports and RNA immunoprecipitation (RIP) were used to verify gene targeting relationships. RESULTS: ERß2 was up-regulated in TNBC tissues and promoted the growth, migration, and invasion of TNBC cells. ERß2 regulated hsa_circ_0000732 expression by binding to SCARF1 promoter. Knockdown of hsa_circ_0000732 inhibited TNBC cell proliferation, migration, and invasion by upregulating miR-1184. CONCLUSION: Our present study found that ERß2 is upregulated in some TNBC cells and promotes TNBC cell growth, migration and invasion by regulating hsa_circ_0000732 targeting miR-1184. The special role of ERß2 in TNBC may be the breakthrough of a targeted treatment strategy for TNBC.

Circular RNAs in renal cell carcinoma: Functions in tumorigenesis and diagnostic and prognostic potentials.

Circular RNAs (circRNAs) are non-coding RNAs with closed ends which makes them resistant to degrading enzyme RNAse R. These RNA molecules show cell, tissue or organ specific expression. Regulatory functions have been reported for a number of circRNAs. Particularly, they have been found to affect cell cycle and control cell proliferation. CircRNAs are involved in physiological processes like natural organ development. Their dysregulation in high-throughput technologies have been shown in a growing number of diseases especially many types of cancers such as renal cell carcinoma (RCC). Differentially expressed circRNAs in RCC tissues compared to normal tissues may affect carcinogenesis process. Overexpressed circRNAs promote tumorigenic functions of RCC cell lines while down-regulated transcripts repress them. Both dysregulated circRNAs are correlated with clinicopathological features, prognosis and survival in RCC patients which along with their acceptable diagnostic values suggest them as potential biomarkers in diagnosis or prediction of prognosis of RCC patients. In this review, we have assessed tumorigenic or tumor-suppressing effects of circRNAs and also their diagnostic and prognostic potentials in RCC.

Circ_0007919 exerts an anti-tumor role in colorectal cancer through targeting miR-942-5p/TET1 axis.

Circular RNAs (circRNAs) are key regulators in the development of many cancers. The present study was aimed to investigate the mechanism by which circ_0007919 affected colorectal cancer (CRC) progression.The differentially expressed circRNA was screened out by analyzing the expression profile of circRNAs of CRC tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for detecting the expressions of circ_0007919, miR-942-5p, and ten-eleven translocation 1 (TET1) mRNA in CRC tissues and cell lines. Cell growth and migration were assessed by cell counting kit-8 (CCK-8) 5-bromo-2'-deoxyuridine (BrdU) and scratch assays. Bioinformatics analysis and dual-luciferase reporter assay were conducted to predict and validate the targeted relationships between circ_0007919 and miR-942-5p, as well as between miR-942-5p and TET1 mRNA. Besides, Western blot was conducted for detecting TET1 protein expression in CRC cells. It was revealed that, in CRC tissues and cell lines, circ_0007919 and TET1 expressions were reduced whereas miR-942-5p expression was enhanced. It was also revealed that circ_0007919 overexpression markedly suppressed CRC cell growth and migration. In addition, circ_0007919 could competitively bind with miR-942-5p to increase the expression of miR-942-5p's target gene TET1. Collectively, circ_0007919 inhibits CRC cell growth and migration via regulating the miR-942-5p/TET1 axis. This study helps to better understand the molecular mechanism of CRC progression.

F-circEA1 regulates cell proliferation and apoptosis through ALK downstream signaling pathway in non-small cell lung cancer.

Studies have confirmed that circular RNA (circRNA) has a stable closed structure, which plays an important role in the progression of tumors. Cancers with positive fusion genes can produce associated fusion circRNA (F-cirRNA). However, there are no reports concerning a role for F-circRNA of the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1 (EML4-ALK1) in non-small cell lung cancer (NSCLC). Our study confirmed the existence of fusion circEA1 (F-circEA1) in NCI-H3122 cells (carrying the EML4-ALK1 gene), F-circEA1 was expressed both in the cytoplasm and nucleus as determined by fluorescence in situ hybridization (FISH) and Sanger sequencing. CCK8 and transwell assays showed that F-circEA1 was beneficial to cell proliferation, metastasis, and invasion. Overexpression of F-circEA1 can also promote cell proliferation, migration and invasion in A549 and SPCA1 cells (non-small cell lung cancer cell line not carrying the EML4-ALK1 gene). Interference with F-circEA1, induced cell cycle arrest and promoted apoptosis as determined by flow cytometry, and increased drug sensitivity to crizotinib in H3122 cells. F-circEA1 directly affected the expression of parental gene EML4-ALK1. Further research found that F-circEA1 can affect the downstream signaling pathway of ALK. In vivo, the growth rate of xenogeneic tumors was reduced and the protein expression level of EML4-ALK1 was significantly decreased in transplanted tumors measured by immunohistochemistry (IHC) after interference with F-circEA1. In conclusion, F-circEA1 can be considered as a proto-oncogene that regulates cell proliferation and apoptosis by affecting the expression of the parental gene EML4-ALK1 and its ALK downstream signaling pathway in non-small cell lung cancer.

Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis.

Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ_0092367 to enhance gemcitabine efficacy was tested and the underlying molecular mechanism of circ_0092367 was investigated. The expression levels of circ_0092367, miR-1206, and ESRP1 were measured using qRT-PCR experiments. The effects of circ_0092367, miR-1206, and ESRP1 on PC cell lines exposed to gemcitabine were examined by CCK-8 assays. We performed luciferase assays to determine the relationship between circ_0092367 and miR-1206 and between miR-1206 and ESRP1. We demonstrated that circ_0092367 was significantly downregulated in PC tissues and cell lines, and a high expression of circ_0092367 was associated with improved survival in patients with PC. Gain- and loss-of-function assays revealed that circ_0092367 inhibited epithelial-mesenchymal transition (EMT) phenotypes and sensitized PC cells to gemcitabine treatment in vitro and in vivo. Cytoplasmic circ_0092367 could directly repress the levels of miR-1206 and thus upregulate the expression of ESRP1, thereby inhibiting EMT and enhancing the sensitivity of PC cells to gemcitabine treatment. Our findings show that circ_0092367 plays a crucial role in sensitizing PC cells to gemcitabine by modulating the miR-1206/ESRP1 axis, highlighting its potential as a valuable therapeutic target in PC patients.

Circular RNA circSNX6 promotes sunitinib resistance in renal cell carcinoma through the miR-1184/GPCPD1/ lysophosphatidic acid axis.

Sunitinib resistance is a major challenge in systemic therapy for renal cell carcinoma (RCC). The role of circular RNAs (circRNAs) in regulating sunitinib resistance of RCC is largely unknown. We established sunitinib-resistant RCC cell lines in vivo. Through RNA-sequencing, we identified circSNX6, whose expression is upregulated in sunitinib-resistant cells compared with their parental cells. High circSNX6 expression was correlated with sunitinib resistance and worse oncologic outcomes in a cohort of 81 RCC patients. In vitro and in vivo experiments confirmed that circSNX6 could promote sunitinib resistance in RCC. circSNX6 acts as a molecular "sponge" to relieve the suppressive effect of microRNA (miR)-1184 on its target gene, glycerophosphocholine phosphodiesterase 1 (GPCPD1), which increases intracellular lysophosphatidic acid (LPA) levels and, ultimately, promotes sunitinib resistance in RCC cells. Our findings demonstrated that the circSNX6/miR-1184/GPCPD1 axis had a critical role in regulation of intracellular LPA levels and sunitinib resistance in RCC; they also provide a novel prognostic indicator and promising therapeutic targets.

Roles of circRNAs in cancer chemoresistance (Review).

Circular RNA (circRNA) is a type of endogenous, high­stability, noncoding RNA. circRNAs exhibit various biological functions, and are involved in physiological and pathological processes occurring in various diseases, including cancers. They can not only act as microRNA and protein sponges, but also interact with proteins, translated peptides, and transcriptional and translational regulators, and compete with pre­mRNA splicing. Chemotherapy is one of the most important types of cancer treatment. However, the resistance of cancer cells to chemotherapy is a leading reason for the failure of chemotherapy. It has been reported that circRNAs play important roles in cancer resistance via a number of mechanisms. The functions of the circRNAs provide insight into their roles in chemoresistance pathways. In addition, some circRNAs may serve as novel biomarkers for the diagnosis and prognosis of cancer resistance. Obtaining improved understanding of the molecular regulatory networks featuring circRNAs in tumors and searching for markers for the diagnosis and treatment of cancer resistance are leading issues in circRNA research. The present review introduced the functions of circRNAs, illustrated the mechanisms underlying drug resistance in cancer, described the contributions of circRNAs to this resistance and discussed the potential application of circRNAs in the treatment of drug­resistant cancer. In particular, the review aimed to reveal the main mechanisms of circRNAs in cancer drug resistance, including mechanisms involving drug transport and metabolism, alterations of drug targets, DNA damage repair, downstream resistance mechanisms, adaptive responses and the tumor microenvironment. The findings may provide novel therapeutic targets for clinical treatment of cancer chemoresistance.

Identification of circ_0058357 as a regulator in non-small cell lung cancer cells resistant to cisplatin by miR-361-3p/ABCC1 axis.

BACKGROUND: Drug resistance is a major clinical drawback behind the failure of chemotherapy in non-small cell lung cancer (NSCLC). In this study, we undertook to identify the precise role of circular RNA (circRNA) circ_0058357 in the functional properties of DDP-resistant NSCLC cells. METHODS: Circ_0058357, miR-361-3p and ATP-binding cassette (ABC) subfamily C member 1 (ABCC1) were quantified by qRT-PCR and western blot. Cell survival and viability were gauged by MTT assay. Cell proliferation, apoptosis, invasion and migration were measured by EdU, flow cytometry, transwell and wound-healing assays, respectively. The direct relationship between miR-361-3p and circ_0058357 or ABCC1 was validated by dual-luciferase reporter assay. RESULTS: Our data showed that circ_0058357 was highly expressed in DDP-resistant NSCLC tissues and cells. Inhibition of circ_0058357 repressed cell growth, invasion, migration, and promoted DDP sensitivity and cell apoptosis of H1299/DDP and A549/DDP cells in vitro. Moreover, inhibition of circ_0058357 diminished the growth of A549/DDP cells and sensitized them to the cytotoxic effect of DDP in vivo. Mechanistically, circ_0058357 contained a miR-361-3p binding site and miR-361-3p was identified as a molecular mediator of circ_0058357 regulation. MiR-361-3p suppressed ABCC1 expression by binding to ABCC1 3'UTR, and miR-361-3p-mediated inhibition of ABCC1 affected the growth, invasion, migration, apoptosis and DDP sensitivity of H1299/DDP and A549/DDP cells. Furthermore, circ_0058357 regulated ABCC1 expression by competitively binding to shared miR-361-3p. CONCLUSIONS: Our findings identified that inhibition of circ_0058357 suppresses the growth and metastasis of H1299/DDP and A549/DDP cells and sensitizes them to DDP therapy partially by targeting the miR-361-3p/ABCC1 axis.

Studies on the Role of circRNAs in Osteoarthritis.

OBJECTIVE: Provide a reference to elucidate the mechanism of circRNAs regulating osteoarthritis (OA) and the clinical treatment. METHODS: Herein, articles about circRNAs (hsa-circ) and osteoarthritis in the recent 5 years have been reviewed and the differential expression and regulatory effect of circRNAs in OA deduced. Based on these conclusions and Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the acquired circRNAs, the potential functions and interactions of circRNAs in OA and the involved signaling pathways are discussed. RESULTS: A total of 33 studies meeting the inclusion criteria were included in this study, and 27 circRNAs were upregulated and 8 circRNAs were downregulated in OA. A total of 31 circRNAs were finally included in the PPI, GO, and KEGG analyses. From PPI, 12 map nodes and 7 map edges were interrelated. VWF had the biggest node and edge size. From GO, VWF showed a majority of the functions. From KEGG, circRNAs are enriched in PI3K/AKT, human papillomavirus infection (HPI), and focal adhesion (FA) pathways, and VWF was involved in major pathways. CONCLUSION: We found that most articles about circRNAs regulating OA in the recent 5 years focused on the mechanism, especially the absorption effect of circ-miRNA as sponges in the recent 2 years, while most of the articles about their functions addressed ECM and PI3K, AKT, and mTOR signaling pathways. Future studies might focus on the functions of circRNAs, and circRNA VWF, with preferable functions, interactions, and involvement, can be used as a biological indicator to detect OA in clinical practice.

Biological and clinical implications of metastasis-associated circular RNAs in oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis-associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis-related circRNAs and their interactions with epithelial-mesenchymal transition-associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis.

Circ_0006948 drives the malignant development of bladder cancer via activating the epithelial-mesenchymal transition.

PURPOSE: To detect the expression characteristic of circ_0006948 in bladder cancer (BC), and to analyze its relationship with pathological parameters and prognosis in BC patients. In addition, molecular mechanisms of circ_0006948 on driving the malignant progression of BC by activating epithelial-mesenchymal transition (EMT) was explored. METHODS: Circ_0006948 levels in 72 BC and paracancerous tissues were detected, and their relationship with pathological parameters and prognosis in BC patients was analyzed by chi-square test. After establishing circ_0006948 knockdown model in 253j and T24 cells, phenotype changes were assessed by cell counting kit-8 (CCK-8), transwell and wound healing assay. Regulatory effects of circ_0006948 on EMT-associated gene expressions in BC cells were determined by Western blot. Finally, the interaction between circ_0006948 and N-cadherin was evaluated by rescue experiments. RESULTS: Circ_0006948 was upregulated in BC tissues and cell lines. High level of circ_0006948 indicated advanced tumor stage, high rates of lymph node metastasis and distant metastasis, and poor prognosis in BC. Knockdown of circ_0006948 reduced proliferative and metastatic abilities in BC cells. The key protein in the EMT signaling E-cadherin was upregulated by knockdown of circ_0006948 in BC cells, while N-cadherin, Vimentin, ß-catenin and MMP-9 were downregulated. The interaction between circ_0006948 and N-cadherin was identified, and they were co-responsible for the malignant development of BC. CONCLUSIONS: Circ_0006948 is upregulated in BC samples, and it is closely linked to tumor stage, metastasis and prognosis in BC patients. It drives proliferative and metastatic abilities in BC cells by activating EMT.

hsa_circ_0005721 triggers proliferation, migration and invasion of osteosarcoma by upregulating the linear transcript TEP1.

PURPOSE: This study aimed to illustrate the biological role of hsa_circ_0005721 in the development of osteosarcoma and the molecular mechanism. METHODS: hsa_circ_0005721 levels in 30 pairs of osteosarcoma and non-tumor tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments were conducted to assess the influence of hsa_circ_0005721 on proliferative, metastatic and apoptotic rates of osteosarcoma cells. The downstream target of hsa_circ_0005721 and their co-regulatory mechanism in malignant development of osteosarcoma were analyzed by dual-luciferase reporter assay and rescue experiments, respectively. RESULTS: hsa_circ_0005721 was upregulated in osteosarcoma tissues and cell lines. Knockdown of hsa_circ_0005721 suppressed proliferative and metastatic rates of U-2OS and Saos-2 cells, and stimulated apoptosis. Serving as a ceRNA, hsa_circ_0005721 upregulated the linear transcript TEP1 by competitively binding miR-16-5p, thus exerting its biological functions in regulating osteosarcoma development. CONCLUSIONS: This study for the first time identified the upregulated hsa_circ_0005721 in osteosarcoma, which triggers the malignant development of osteosarcoma by upregulating the linear transcript TEP1.