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The kind of biogenesis of circRNAs: (a) Standard splicing (conventional linear splicing); (b) circRNAs is generated by a process called, Backsplicing: this splicing lead to creating 1) exonic circRNA that can make two forms including single exon circRNA and multiple exon circRNA, 2) Exonic-Intronic circRNA and 3) Intronic circRNA
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Circular RNAs (circRNAs) are a class of long non-coding RNAs (lncRNAs) which have a circular and closed loop structure. They are ubiquitous, stable, conserved and diverse RNA molecules with a range of activities such as translation and splicing regulation, which are able to interacting with RNA-binding proteins and specially miRNA sponge. The expre...
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Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for c...
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... It has been shown that circRNA serves as miRNA sponge to regulate target genes (Lv et al. 2021;Xiong et al. 2018). The application of circRNA in cancer has become a research hotspot, and it is expected to become a molecular therapeutic target for cancers (Shabaninejad et al. 2019;Patop and Kadener 2018). At present, many high expression of circRNAs have been found to facilitate BCa malignant progression (Chen et al. 2021a;Yu et al. 2021a). ...
Circular RNA (circRNA) has been reported to regulate the development of bladder cancer (BCa). However, the role of circ_0000758 in BCa progression is unknown. Circ_0000758 and miR-1236-3p expression, as well as ZEB2 mRNA expression were determined by qRT-PCR. BCa cell biological functions were determined by MTT assay, EdU assay, flow cytometry, wound healing assay and tube formation assay. Protein expression was detected by western blot analysis. RNA pull-down assay and dual-luciferase reporter assay were used to confirm RNA interaction. Xenograft mice models were constructed to assess the effect of circ_0000758 on BCa tumor growth. Circ_0000758 had increased expression in BCa tissues and cells. Circ_0000758 silencing could inhibit BCa cell growth, migration, angiogenesis in vitro, and tumor growth in vivo. Circ_0000758 served as a molecular sponge for miR-1236-3p, and miR-1236-3p inhibitor reversed circ_0000758 knockdown-mediated the inhibition effect on BCa cell progression. ZEB2 was targeted by miR-1236-3p, and its overexpression also revoked the suppressive effect of miR-1236-3p on BCa cell growth, migration, and angiogenesis. Besides, circ_0000758 knockdown also restrained BCa tumor growth. Circ_0000758 might promote BCa cell growth, migration, and angiogenesis by regulating the miR-1236-3p/ZEB2 axis.
... 9 Unlike standard linear RNA, circRNA forms a covalently closed, continuous stable loop, with no 5 0 end cap and 3 0 end poly (A) tail, therefore, it is resistant to exonuclease digestion. 10,11 Most circRNAs, abundant and conserved in different species, has specific expression in tissues or developmental stages. 9 Studies have revealed that circRNAs act in various cancers and can be used as better predictive biomarkers as well as a therapeutic targets for cancer treatment. ...
Previous studies have proved circFN1 is highly expressed in acute myeloid leukemia (AML) patients and AML cell lines. This study aims to investigate the impact of circFN1 on AML and its mechanism. Via real‐time quantitative PCR to detect circFN1, miR‐1294, ARHGEF10L expressions in clinical plasma samples and AML cell lines, AML cells were cultured in vitro and transfected with si‐circFN1, pcDNA3.1‐circFN1, and si‐ARHGEF10L, respectively, or co‐transfected pcDNA3.1‐circFN1 + miR‐1294 mimic and pcDNA3.1‐circFN1 + si‐ARHGEF10L. Using dual luciferase reporter experiment to detect the relationship between circFN1 and miR‐1294, as well as miR‐1294 and ARHGEF10L. CCK‐8 was used to detect cell proliferation, Transwell to cell invasion, TUNEL staining and flow cytometry to detect cell apoptosis, RT‐qPCR to circFN1 RNA, miR‐1294, and ARHGEF10L expression levels in HL‐60 cells, and western blot to ARHGEF10L protein expression level in HL‐60 cells. We found highly expressed circFN1 and ARHGEF10L, as well as low‐expressed miR‐1294 in AML patients and AML cell lines. In contrast to si‐NC group, si‐circFN1 group could signally inhibit HL‐60 cell proliferation and migration, but promote cell apoptosis; compared with mimic NC group, miR‐1294 mimic group could visually inhibit HL‐60 cell proliferation and migration, but promote cell apoptosis. miR‐1294 was the target of circFN1, and ARHGEF10L was the target of miR‐1294. Over‐expressing miR‐1294 or silencing ARHGEF10L could signally inhibit circFN1 promoting HL‐60 cell proliferation and migration and repressing cell apoptosis. circFN1 promotes proliferation and invasion of AML cell and represses cell apoptosis via regulating miR‐1294/ARHGEF10L axis, which provides new insight for molecular targeted‐treatment for AML.
... According to previous studies, circRNAs influence various biological processes, are persistent and are concentrated in exosomes (69,70). Exosomal circPRRX1, as the competing endogenous RNA of miR-596, has been revealed to promote the proliferation, migration and invasion of GC cells, and decreases their radiation sensitivity through the upregulation of NF-κB-activated protein (71). ...
Gastrointestinal cancer is frequently detected at an advanced stage and has an undesirable prognosis due to the absence of efficient and precise biomarkers and therapeutic targets. Exosomes are small, living‑cell‑derived vesicles that serve a critical role in facilitating intercellular communication by transporting molecules from donor cells to receiver cells. circular RNAs (circRNAs) are mis‑expressed in a variety of diseases, including gastrointestinal cancer, and are promising as diagnostic biomarkers and tumor therapeutic targets for gastrointestinal cancer. The main features of exosomes and circRNAs are discussed in the present review, along with research on the biological function of exosomal circRNAs in the development and progression of gastrointestinal cancer. It also assesses the advantages and disadvantages of implementing these findings in clinical applications.
... In recent years, growing evidence has shown that non-coding RNAs play an essential role in gene expression regulation, and dysregulation of many of these RNAs lead to diseases, including cancers. Non-coding RNAs can act as tumor suppressors [10,11], while many others behave as oncogenes [12][13][14][15][16][17], or some RNA species can be both depending on the circumstances [18]. Recently, miR122-5p has been shown to act as an oncogene by targeting the 3' untranslated region (3'UTR) of RBEL1A's mRNA to up-regulate its expression, but this up-regulation can be disrupted by androgen receptor [8]. ...
Research on Rab-like protein 1A (RBEL1A) in the past two decades highlighted the oncogenic properties of this gene. Despite the emerging evidence, its importance in cancer biology was underrated. This is the first RBEL1A critical review covering its discovery, biochemistry, physiological functions, and clinical insights. RBEL1A expression at the appropriate levels appears essential in normal cells and tissues to maintain chromosomal stability; however, its overexpression is linked to tumorigenesis. Furthermore, the upstream and downstream targets of the RBEL1A signaling pathways will be discussed. Mechanistically, RBEL1A promotes cell proliferation signals by enhancing the Erk1/2, Akt, c-Myc, and CDK pathways while blunting the apoptotic signals via inhibitions on p53, Rb, and caspase pathways. More importantly, this review covers the clinical relevance of RBEL1A in the cancer field, such as drug resistance and poor overall survival rate. Also, this review points out the bottle-necks of the RBEL1A research and its future research directions. It is becoming clear that RBEL1A could potentially serve as a valuable target of anticancer therapy. Genetic and pharmacological researches are expected to facilitate the identification and development of RBEL1A inhibitors as cancer therapeutics in the future, which could undoubtedly improve the management of human malignancy.
... They are divided into two primary categories (I)-Regulatory ncRNAs, which are made up of tRNAs, rRNAs, snoRNAs, and snRNAs, are housekeeping ncRNAs (II) regulatory non-coding RNAs (ncRNAs) may be divided into two groups based on the nucleotide fragment length those with transcripts of less than 200 nucleotides, including certain microRNAs (miR-NAs) and siRNAs, and those with transcripts of more than 200 nucleotides, known as long non-coding RNAs (lncR-NAs). Circular RNAs (circRNAs) are lncRNAs that have a wide variety of lengths between hundreds and thousands of nucleotides (Hombach and Kretz 2016;Shabaninejad et al. 2019).CircNOL10 is a circular RNA that is expressed at low concentrations in lung cancer, although its roles in lung cancer are unclear.CircNOL10 increases the synthesis of the transcriptional factor sex comb on midleg-like 1 (SCML1) and thereby regulates SCML1 regulation of the humanin (HN) polypeptide family by blocking transcription factor ubiquitination. circNOL10 also affects mitochondrial activity by modulating the humanin polypeptide family and impacting various signalling pathways, eventually lowering cell proliferation and cell cycle progression and inducing apoptosis in lung cancer cells, limiting lung cancer formation. ...
The peptides are known to have diverse therapeutic indications and help cure many disease conditions. The mitochondrial genome comprises a novel class of micro peptides with various biological effects. Human mitochondrial peptides are among those that have a favourable impact on medicinal applications. Mitochondrial-derived peptides are small therapeutic peptides transcribed through mitochondrial DNA open-reading frames. Humanin is a mitochondrial peptide inhibiting complex I activity and reducing oxidative stress. It has significant apoptosis activity; therefore, it acts as an anti-apoptotic agent in the testis, boosting its reproductive role. It primarily affects cardioprotective and neuroprotective pathways, which operate as Alzheimer’s disease treatment agents. SHLPs and humanin were derived from mitochondrially encoded 16s rRNA small open reading frames. This peptide enhances mitochondrial functions and the survival of cells in response to oxidative stress. SHLP (1–6) has distinct and overlapping functions with humanin which regulate cell viability. The anti-diabetic activity is present in SHLP 2 and 3, which are insulin-resistant. Likewise, SHLP-6 has an apoptotic effect on cancer cells while it protects the cells against mitochondrial-mediated apoptosis. The mitochondrial-derived peptides increase insulin sensitivity, stimulating glucose absorption through peripheral tissues while decreasing glucose synthesis in the liver. These peptides are helpful in the treatment of multiple diseases. Thus, in this review discusses the mitochondrial peptide-humanin and SHLP types and their therapeutic potential.
... The majority of circRNAs are highly expressed in the cytoplasm [234][235][236][237][238][239][240]. CircRNAs contain covalently closed-loop structures, which makes them more stable relative to linear RNAs [241]. ...
Prostate cancer (PCa) is known as one of the most prevalent malignancies globally and is not yet curable owing to its progressive nature. It has been well documented that Genetic and epigenetic alterations maintain mandatory roles in PCa development. Apoptosis, a form of programmed cell death, has been shown to be involved in a number of physiological processes. Apoptosis disruption is considered as one of the main mechanism involved in lots of pathological conditions, especially malignancy. There is ample of evidence in support of the fact that microRNAs (miRNAs) have crucial roles in several cellular biological processes, including apoptosis. Escaping from apoptosis is a common event in malignancy progression. Emerging evidence revealed miRNAs capabilities to act as apoptotic or anti-apoptotic factors by altering the expression levels of tumor inhibitor or oncogene genes. In the present narrative review, we described in detail how apoptosis dysfunction could be involved in PCa processes and additionally, the mechanisms behind miRNAs affect the apoptosis pathways in PCa. Identifying the mechanisms behind the effects of miRNAs and their targets on apoptosis can provide scientists new targets for PCa treatment.
... Circular RNA (circRNA), a type of single-stranded closedloop RNA, is increasingly appreciated to play important roles in gene transcription and translation [2] largely by adsorbing miRNAs. Differentially expressed circRNAs have been identified in OC. circRNAs play multiple critical roles in OC biological behavior, including tumor invasion, migration, metastasis, angiogenesis, and resistance to cisplatin chemotherapy [3] [4]. ...
... Downregulation of circSnx12, which negatively regulates ferroptosis by adsorbing miR-224-5p, has been implicated in the molecular mechanism of heart failure in an aortal-ligation mouse model [9], suggesting a number of novel targets for overcoming 4 chemoresistance in OC. In this study, we sought to understand the biological role of circSnx12 in DDP-resistant OC cells and tissues. ...
Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.
... miRNAs are small non-coding RNAs of 18-25 nucleotides in length which are involved in the post-transcriptional regulation of gene expression [46,47]. They are found to be aberrantly expressed in many pathological conditions, including cancer, and can be detected in bodily fluids including urine, sputum, and blood, making them exciting biomarkers for cancer detection [48,49]. ...
... We also include the experimental models in these studies, such as the cell lines used. Since comprehensive reviews on circRNA functions have been published recently [10,123,124], we focus on circRNAs that are strongly dysregulated in EOC and have been studied using multiple model systems, especially animal models, and discuss their therapeutic potential. In vitro: ↓ proliferation/invasion/migration/EMT In vivo: ↓ tumor growth miR-630/RASSF8 [189] Abbreviations: EMT, epithelial-mesenchymal transition; MMT, mesothelial-to-mesenchymal transition; DDP, cisplatin; PTX, paclitaxel; s.c., subcutaneous injection; i.p., intraperitoneal injection; i.v., intravenous injection; ↑ increased; ↓ decreased; * circBase ID was not reported by the study; # The circRNA name reported was converted to circBase ID through the website: http://www.bio-inf.cn/CircIDTrans.aspx ...
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, and more than 70% of patients are diagnosed at advanced stages. Despite the application of surgery and chemotherapy, the prognosis remains poor due to the high relapse rate. It is urgent to identify novel biomarkers and develop novel therapeutic strategies for EOC. Circular RNAs (circRNAs) are a class of noncoding RNAs generated from the “back-splicing” of precursor mRNA. CircRNAs exert their functions via several mechanisms, including acting as miRNA sponges, interacting with proteins, regulating transcription, and encoding functional proteins. Recent studies have identified many circRNAs that are dysregulated in EOC and may be used as diagnostic and prognostic markers. Increasing evidence has revealed that circRNAs play a critical role in ovarian cancer progression by regulating various cellular processes, including proliferation, apoptosis, metastasis, and chemosensitivity. The circRNA-based therapy may be a novel strategy that is worth exploring in the future. Here, we provide an overview of EOC and circRNA biogenesis and functions. We then discuss the dysregulations of circRNAs in EOC and the possibility of using them as diagnostic/prognostic markers. We also summarize the role of circRNAs in regulating ovarian cancer development and speculate their potential as therapeutic targets.
... Also, miRNAs transfer genetic information between different cells or even from one tissue to another [18,19]. The miRNAs have therapeutic advantages, especially in certain diseases that may not be developed by a single genetic link [22,23]. Many investigations have shown that a number of miRNAs are clinically important as biomarkers. ...
Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of mortality among men. The recurrent reports of false-positive results of common PCa biomarkers have led to the introduction of some promising biomarkers for PCa, such as exosomal non-coding RNAs (ncRNAs). Exosomes contain various components, such as several ncRNAs (miRNAs and lncRNAs), which are important in the initiation and progression of PCa. These ncRNAs also reflect the state of the origin cell. In this article, we reviewed research on the importance and roles of ncRNAs in PCa, focusing on exosomal ncRNAs. We highlighted plasma exosomal miRNAs (8 miRNAs), urine exosomal miRNAs (19miRNAs), serum miRNAs (2 miRNAs), and five miRNAs in semen used for PCa diagnosis. Also, four exosomal lncRNAs in plasma and urine can be used as biomarkers for PCa diagnosis.
