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Journal ArticleDOI

CircRNA_102272 Promotes Cisplatin-Resistance in Hepatocellular Carcinoma by Decreasing MiR-326 Targeting of RUNX2.

07 Dec 2020-Cancer management and research (Dove Press)-Vol. 12, pp 12527-12534
TL;DR: CircRNA_102272 is significantly increased in HCC tissues and cells and promotes HCC cell proliferation and cisplatin-resistance and acts as a ceRNA to suppress the expression and activity of miR-326, leading to the increase in RUNX2 expression.
Abstract: Background Hepatocellular carcinoma (HCC) is the leading cause of tumor-associated death in males and females worldwide. HCC is mostly diagnosed at advanced stages and the chemotherapeutic cisplatin is one of the major therapeutic options in the treatment of patients with treating advanced HCC. Despite several reports on HCC multidrug resistance, the underlying regulatory mechanisms are still unclear. Methods RT-PCR was performed to detect circRNA_102272, miR-326 and RUNX2 expression. The CCK8 assay was used to examine cell proliferation and cisplatin IC50 values. The luciferase reporter assay was performed to verify complementary combinations between circRNA_102272 and miR-326 and between miR-326 and RUNX2. Results CircRNA_102272 expression was upregulated in HCC tissues and cells. CircRNA_102272 knockdown suppressed HCC cell proliferation and decreased cisplatin-resistance. In addition, circRNA_102272 facilitated HCC cisplatin-resistance by regulating the miR-326/RUNX2 axis. Conclusion CircRNA_102272 is significantly increased in HCC tissues and cells and promotes HCC cell proliferation and cisplatin-resistance. More importantly, circRNA acts as a ceRNA to suppress the expression and activity of miR-326, leading to the increase in RUNX2 expression. By elucidating circRNA_102272 role and mechanism of action in HCC, our study provides insights and an opportunity to overcome cisplatin-resistance in HCC.

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Citations
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Journal ArticleDOI
TL;DR: In this article, the role of Wnt signaling in hepatocellular carcinoma (HCC) and its association with progression and therapy response based on pre-clinical and clinical evidence is discussed.
Abstract: Liver cancers cause a high rate of death worldwide and hepatocellular carcinoma (HCC) is considered as the most common primary liver cancer. HCC remains a challenging disease to treat. Wnt/β-catenin signaling pathway is considered a tumor-promoting factor in various cancers; hence, the present review focused on the role of Wnt signaling in HCC, and its association with progression and therapy response based on pre-clinical and clinical evidence. The nuclear translocation of β-catenin enhances expression level of genes such as c-Myc and MMPs in increasing cancer progression. The mutation of CTNNB1 gene encoding β-catenin and its overexpression can lead to HCC progression. β-catenin signaling enhances cancer stem cell features of HCC and promotes their growth rate. Furthermore, β-catenin prevents apoptosis in HCC cells and increases their migration via triggering EMT and upregulating MMP levels. It is suggested that β-catenin signaling participates in mediating drug resistance and immuno-resistance in HCC. Upstream mediators including ncRNAs can regulate β-catenin signaling in HCC. Anti-cancer agents inhibit β-catenin signaling and mediate its proteasomal degradation in HCC therapy. Furthermore, clinical studies have revealed the role of β-catenin and its gene mutation (CTNBB1) in HCC progression. Based on these subjects, future experiments can focus on developing novel therapeutics targeting Wnt/β-catenin signaling in HCC therapy.

46 citations

Journal ArticleDOI
TL;DR: In this paper , the authors identified a functional RNA, hsa_circ_0000384 (circMRPS35), from public tumor databases using a set of computational analyses, and further identified that circMRPS 35 was highly expressed in 35 pairs of HCC from patients.

30 citations

Journal ArticleDOI
TL;DR: In this paper, the authors identified a functional RNA, hsa_circ_0000384 (circMRPS35), from public tumor databases using a set of computational analyses, and further identified that circMRPS 35 was highly expressed in 35 pairs of HCC from patients.

30 citations

Journal ArticleDOI
TL;DR: In vivo tumor xenograft experiments showed that knockdown ofcircZFR inhibited tumor growth and weakened DDP resistance, while CAFs-derived exosomes incubation increased the expression of circZFR, inhibited the STAT3/NF-κB pathway, promoted tumor growth, and enhanced DDP Resistance.
Abstract: ABSTRACT Chemoresistance in hepatocellular carcinoma (HCC) has been found to be influenced by exosomal transport of circRNAs. However, the role of circZFR in HCC chemoresistance still remains unclear. In the present study, circZFR was highly expressed in cisplatin (DDP)-resistant HCC cell lines and could regulate DDP resistance of the HCC cells. Also, circZFR was highly expressed in cancer-associated fibroblast (CAFs) and the exosome of CAFs. In addition, supplementation of CAFs in culture medium could promote DDP resistance of HCC cells. In vivo tumor xenograft experiments showed that knockdown of circZFR inhibited tumor growth and weakened DDP resistance, while CAFs-derived exosomes incubation increased the expression of circZFR, inhibited the STAT3/NF-κB pathway, promoted tumor growth, and enhanced DDP resistance. In general, CAFs-derived exosomes deliver circZFR to HCC cells, inhibit the STAT3/NF-κB pathway, and promote HCC development and chemoresistance. The results provided a new sight for the prevention and treatment of chemoresistance in HCC. Graphical abstract

22 citations

Journal ArticleDOI
Sha Qin1, Yitao Mao1, Xue Chen1, Juxiong Xiao1, Yan Qin1, Luqing Zhao1 
TL;DR: In this article, the authors elucidated the biological functions and molecular mechanisms of m6A modification in the carcinogenesis of HCC by illustrating three different regulatory factors ("writer", "eraser", and "reader") of the modification process.
Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. HCC has high rates of death and recurrence, as well as very low survival rates. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNAs, and circRNAs are a class of circular noncoding RNAs that are generated by back-splicing and they modulate multiple functions in a variety of cellular processes. Although the carcinogenesis of HCC is complex, emerging evidence has indicated that m6A modification and circRNA play vital roles in HCC development and progression. However, the underlying mechanisms governing HCC, their cross-talk, and clinical implications have not been fully elucidated. Therefore, in this paper, we elucidated the biological functions and molecular mechanisms of m6A modification in the carcinogenesis of HCC by illustrating three different regulatory factors ("writer", "eraser", and "reader") of the m6A modification process. Additionally, we dissected the functional roles of circRNAs in various malignant behaviors of HCC, thereby contributing to HCC initiation, progression and relapse. Furthermore, we demonstrated the cross-talk and interplay between m6A modification and circRNA by revealing the effects of the collaboration of circRNA and m6A modification on HCC progression. Finally, we proposed the clinical potential and implications of m6A modifiers and circRNAs as diagnostic biomarkers and therapeutic targets for HCC diagnosis, treatment and prognosis evaluation.

17 citations

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Journal ArticleDOI
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Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.

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Journal ArticleDOI
TL;DR: A new role for circRNAs in regulating gene expression in the nucleus is revealed, in which EIciRNAs enhance the expression of their parental genes in cis, and a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EICIRNAs is highlighted.
Abstract: Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA sponges in animal cells Here, we report a class of circRNAs associated with RNA polymerase II in human cells In these circRNAs, exons are circularized with introns 'retained' between exons; we term them exon-intron circRNAs or EIciRNAs EIciRNAs predominantly localize in the nucleus, interact with U1 snRNP and promote transcription of their parental genes Our findings reveal a new role for circRNAs in regulating gene expression in the nucleus, in which EIciRNAs enhance the expression of their parental genes in cis, and highlight a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EIciRNAs

2,077 citations

Journal ArticleDOI
01 Feb 2012-PLOS ONE
TL;DR: By deep sequencing of RNA from a variety of normal and malignant human cells, this work suggests that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.
Abstract: Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.

1,989 citations

Journal ArticleDOI
TL;DR: Evidence is emerging that some circRNAs might regulate microRNA (miRNA) function, and roles in transcriptional control have also been suggested.
Abstract: Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed comprehensive studies of circular RNA species Recent studies have revealed thousands of endogenous circular RNAs in mammalian cells, some of which are highly abundant and evolutionarily conserved Evidence is emerging that some circRNAs might regulate microRNA (miRNA) function, and roles in transcriptional control have also been suggested Therefore, study of this class of noncoding RNAs has potential implications for therapeutic and research applications We believe the key future challenge for the field will be to understand the regulation and function of these unusual molecules

1,954 citations

Journal ArticleDOI
TL;DR: Hsa_circ_0025202 served an anti-oncogenic role in HR-positive breast cancer, and it could be exploited as a novel marker for tamoxifen-resistant breast cancer.

265 citations