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      CircRNA_400029 promotes the aggressive behaviors of cervical cancer by regulation of miR-1285-3p/TLN1 axis

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          Abstract

          Background: Cervical cancer (CC) is the highest incidence of female malignant tumor in China. Circular RNAs (circRNAs) has been reported to affect CC progression by altering mRNA stability at the transcriptional level or binding to miRNAs to produce competitive endogenous RNA (ceRNA). For this purpose, our study was aimed to investigate the function effects and the potential regulatory mechanism of the circRNA_400029 in CC cells.

          Materials and methods: The expression levels of circRNA_400029 and miR-1285-3p were detected by real time polymerase chain reaction (RT-PCR). Similarly, the mRNA and protein levels of TLN1 (Talin 1) was detected by RT-PCR and Western blot. Cell-Counting Kit-8 (CCK-8), EdU and Flow cytometry assay were used to detect cell proliferation, cell cycle and apoptosis. Then the Transwell assays were used to test cell migration and invasion. Besides this, the functional targets were confirmed by Dual luciferase reporter assays. Tumor xenograft in nude mice checked the result in vivo.

          Results: To begin with, circRNA_400029 was upregulated in CC cells and tissue. Knockdown circRNA_400029 inhibited cell proliferation, migration and invasion while induced cell apoptosis. Interestingly, miR-1285-3p targeted circRNA_400029 and down-regulated of miR-1285-3p could reverse the effects of circRNA_400029 weak-expression on progression and apoptosis of CC cells. Moreover, TLN1 was up-regulated in CC cells and identified as a direct target of miR-1285-3p. Meanwhile, we found that miR-1285-3p negatively regulated the function of TLN1. Finally, the circRNA_400029/miR-1285-3p/TLN1 axis could affect tumor growth in vivo.

          Conclusion: The overexpressed circRNA_400029 promoted CC proliferation, migration and invasion while deduced apoptosis by sponging miR-1285-3p to regulate TLN1. CircRNA_400029 was a potential onco-circRNA in CC, and might be a promised therapy target.

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          Most cited references34

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          Cancer statistics, 2020

          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 population-based cancer occurrence. Incidence data (through 2016) 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 (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
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            The Biogenesis, Functions, and Challenges of Circular RNAs

            Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal machinery and can be modulated by both cis complementary sequences and protein factors. The functions of most circRNAs remain largely unexplored, but known functions include sequestration of microRNAs or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. However, challenges exist at multiple levels to understanding of the regulation of circRNAs because of their circular conformation and sequence overlap with linear mRNA counterparts. In this review, we survey the recent progress on circRNA biogenesis and function and discuss technical obstacles in circRNA studies.
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              Past, present, and future of circ RNA s

              Exonic circular RNAs (circRNAs) are covalently closed RNA molecules generated by a process named back-splicing. circRNAs are highly abundant in eukaryotes, and many of them are evolutionary conserved. In metazoans, circular RNAs are expressed in a tissue-specific manner, are highly stable, and accumulate with age in neural tissues. circRNA biogenesis can regulate the production of the linear RNA counterpart in cis as back-splicing competes with linear splicing. Recent reports also demonstrate functions for some circRNAs in trans: Certain circRNAs interact with microRNAs, some are translated, and circRNAs have been shown to regulate immune responses and behavior. Here, we review current knowledge about animal circRNAs and summarize new insights into potential circRNA functions, concepts of their origin, and possible future directions in the field.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2022
                1 January 2022
                : 13
                : 2
                : 541-553
                Affiliations
                Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P. R. China.
                Author notes
                ✉ Corresponding author: Dan-bo Wang, Department of Gynecology, Liaoning Province Cancer Hospital & Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province 110042, China. E-mail: wangdanbo@ 123456cancerhosp-ln-cmu.com .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav13p0541
                10.7150/jca.61437
                8771527
                35069901
                28d09ab8-6076-451f-a826-8b98450eed24
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 9 April 2021
                : 11 October 2021
                Categories
                Research Paper

                Oncology & Radiotherapy
                cervical cancer,circrna_400029,mir-1285-3p,tln1,proliferation,invasion
                Oncology & Radiotherapy
                cervical cancer, circrna_400029, mir-1285-3p, tln1, proliferation, invasion

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