Regulatory mechanisms and clinical perspectives of circRNA in digestive system neoplasms

Sun, Zhenqiang; Chen, Chen; Su, Yinan; Wang, Weiwei; Yang, Shenghong; Zhou, Quanbo; Wang, Guixian; Li, Zhen; Song, Junmin; Zhang, Zhiyong; Yuan, Weitang; Wang, Zhibin

doi:10.7150/jca.31167

Cited by 31 publications

(19 citation statements)

References 72 publications

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“…Emerging evidence indicates that circular RNA may be an attractive treatment target for cancer metastasis. Previous studies suggest that circRNAs may function as miRNA sponges, translate to proteins, or interact with RNA-binding protein to regulate their downstream targets 22 , 23 . Our FISH and nuclear/cytoplasmic fraction analyses revealed that circ-0046263 was mainly located in the cytoplasm, indicating that it may act as miRNA sponges.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3

Chen

et al. 2020

Cell Death Dis

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Accumulating evidences indicate that circular RNAs (circRNAs), a subclass of noncoding RNAs, play important role in regulating gene expression in eukaryotes. Hsa_circ_0046263 (circ-0046263) was found aberrantly expressed in nasopharyngeal carcinoma (NPC), but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, RNase R assay, and nucleic acid electrophoresis were conducted to verify the identification of circ-0046263. Nuclear separation and fluorescence in situ hybridization (FISH) assays were used to determine the localization of circ-004263. Dual luciferase reporter and RNA immunoprecipitation (RIP) were employed to confirm the binding of circ-0046263 with miR-133a-5p. Colony formation, proliferation, wound healing, transwell, western blot, and in vivo tumor growth and metastasis assays were performed to assess the roles of circ-0046263, miR-133a-5p, IGFBP3 and their interactions in NPC cells. Circ-0046263 was upregulated in both NPC cell lines and tissues. The in vitro functional studies revealed that knockdown of circ-0046263 inhibited the proliferation, invasion, and migration of NPC cells, whereas its overexpression produced the opposite result. In vivo experiments indicated that knockdown or overexpression of circ-0046263 attenuated or promoted tumor growth and metastasis, respectively. Mechanistically, circ-0046263 could act as a miRNA sponge to absorb miR-133a-5p and upregulate the expression of miRNA downstream target IGFBP3. In addition, miR-133a-5p inhibition or IGFBP3 overexpression could rescue the malignant behavior induced by circ-0046263 silencing. Finally, circ-0046263 plays a tumor-promoting role in NPC to enhance malignant behavior through the miR-133a-5p/IGFBP3 axis, which could be a potential target for NPC therapy.

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Section: Discussionmentioning

confidence: 99%

Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3

Chen

et al. 2020

Cell Death Dis

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“…Recently, circRNAs have been proved to be rich in conserved miRNA response elements (MREs), and act as competing endogenous RNAs (ceRNAs) or natural miRNA sponges in regulating gene expression, they communicate with and co-regulate each other by competing for binding to shared miRNA [ 19 ]. Exon circRNAs are mainly found in the cytoplasm and act as an miRNA sponge [ 20 ], while ciRNAs and EIciRNAs are thought to be regulators of parental gene in the cis/transcribed nucleus [ 21 ]. Some circRNAs can also regulate gene expression by competitive alternative splicing or by acting as a translation template [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Expression Analysis of Circular RNAs in Young and Sexually Mature Boar Testes

Zhang

Wei

et al. 2021

Animals

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Testicular development is critical for male animals’ reproduction and is tightly regulated by epigenetic factors. Circular RNAs (circRNAs) were recently identified in the testes of humans and bulls. However, the expression profile of circRNAs and their potential biological functions in boar testicular development remain unclear. We identified 34,521 and 31,803 circRNAs in piglet (30 d) and adult (210 d) boar testes by high-throughput sequencing, respectively. Bioinformatics analysis revealed that these circRNAs are widely distributed on autosomes and sex chromosomes. Some of the host genes can generate multiple circRNAs. A total of 2326 differentially expressed circRNAs (DECs) derived from 1526 host genes was found in testicular development, of which 1003 circRNAs were up-regulated in adult boar testes and 1323 circRNAs were down-regulated. Furthermore, gene ontology analysis of host genes of DECs revealed that these circRNAs are mainly involved in regulating spermatogenesis, cilia motility, and hormone biosynthesis. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DECs are markedly enriched to stem cell pluripotency regulation, tight junctions, adhesion junctions, and cAMP signaling pathway. These results indicate that circRNAs are abundantly expressed in boar testes and exhibit dynamic changes during testicular development.

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“…Also, a covalently closed ring structure is possessed by circRNAs. Therefore, they are insensitive to exonuclease R and stable expression 24 .…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0029693 (circ-LATS2) promotes cell proliferation and regulates WNT5A via miR-4686 in breast cancer cells.

Hu¹,

Hua²,

Ji³

et al. 2020

Preprint

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Background: Breast cancer (BC) is the most malignant form of tumor in women, which threatens females’ health. Circular RNAs (circRNAs), a class of non-coding RNAs, can act as a disease biomarker and endogenous “sponge” molecules for microRNAs (miRNAs). circRNAs may also influence the expression of their parent gene. LATS2 is a vital suppressor gene in Hippo pathway, which is a signaling cascade composed of a group of conserved kinases. The Hippo pathway plays an important role in almost all cancer types. Methods: Colony formation assays, MTT assays, wound healing assays, xenografts mice experiment, qRT-PCR, western blot assays, immunohistochemical staining assays, dual-luciferase reporter assays and Fluorescence in situ hybridization. Student’s t-test was used to analyse the results.Results: We discovered that circular RNA hsa_circ_0029693 (circ-LATS2), an exonic circRNA, are highly expressed in breast cancer cells. Furthermore, in BC patients’ samples, higher expression of circ-LATS2 was significantly related to higher percentage of Ki-67 expression; however the expression of circ-LATS2 was higher in HER2 negative BC patients compared to HER2 positive ones. We investigated the potential function and mechanism of circ-LATS2 action in BC. The results suggested that circ-LATS2 promoted cell proliferation, growth and migration. Through western blot and immunohistochemical staining assays, we found that circ-LATS2 could influence LATS2 expression. We also discovered that there was an inverse expression relationship between miR-4686 and circ-LATS2, suggesting that circ-LATS2 might act as an endogenous “sponge” for miR-4686. Using dual-luciferase reporter assays, we confirmed that circ-LATS2 can bind miR-4686. Increased miR-4686 expression caused a reduction in the protein levels of WNT5A, which is a putative target of miR-4686. We confirm this using dual-luciferase reporter assays that revealed that miR-4686 targets WNT5A by binding its 3’-untranslated region (3’UTR). Conclusions: Our results showed that circ-LATS2 expression in BC patients’ samples were significantly related to Ki-67 expression. In addition, circ-LATS2 acted as a promoter of proliferation and growth of breast cancer cells. These indicated that circ-LATS2 is a proliferative factor, similar to Ki-67; it also acts as a co-biomarker with Ki-67 in clinical treatment.

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Regulatory mechanisms and clinical perspectives of circRNA in digestive system neoplasms

Cited by 31 publications

References 72 publications

Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3

Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3

Expression Analysis of Circular RNAs in Young and Sexually Mature Boar Testes

Hsa_circ_0029693 (circ-LATS2) promotes cell proliferation and regulates WNT5A via miR-4686 in breast cancer cells.

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