Accentuating CircRNA-miRNA-Transcription Factors Axis: A Conundrum in Cancer Research.

Deepti Singh,Nabil A Alhakamy,Hifzur R Siddique,Prashant Kesharwani

doi:10.3389/fphar.2021.784801

Deepti Singh, Nabil A Alhakamy + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2021.784801

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Abstract

Circular RNAs (circRNAs) are the newly uncovered class of non-coding RNAs being cognized as profound regulators of gene expression in developmental and disease biology. These are the covalently closed RNAs synthesized when the pre-mRNA transcripts undergo a back-splicing event. In recent years, circRNAs are gaining special attention in the scientific world and are no longer considered as “splicing noise” but rather structurally stable molecules having multiple biological functions including acting as miRNA sponges, protein decoys/scaffolds, and regulators of transcription and translation. Further, emerging evidence suggests that circRNAs are also differentially expressed in multiple cancers where they play oncogenic roles. In addition, circRNAs in association with miRNAs change the expression patterns of multiple transcription factors (TFs), which play important roles in cancer. Thus, the circRNA-miRNA-TFs axis is implicated in the progression or suppression of various cancer types and plays a role in cell proliferation, invasion, and metastasis. In this review article, we provide an outline of the biogenesis, localization, and functions of circRNAs specifically in cancer. Also, we highlight the regulatory function of the circRNA-miRNA-TFs axis in the progression or suppression of cancer and the targeting of this axis as a potential therapeutic approach for cancer management. We anticipate that our review will contribute to expanding the knowledge of the research community about this recent and rapidly growing field of circRNAs for further thorough investigation which will surely help in the management of deadly disease cancer.

Highlights

Cancer involves a broad range of dysregulations in the genome, transcriptome, and proteome
The circ-Homeodomain Interacting Protein Kinase 3 (HIPK3) is another circular RNAs (circRNA) that acts as a competing endogenous RNA and functions in cancer progression and metastasis via sponging miR-338-3p and enhancing the Hypoxia-inducible factor-1α (HIF-1α) levels resulting in HIF-1α mediated Epithelial state to mesenchymal state (EMT) of cervical cancer (Qian et al, 2020)
Cancer-related available database RNA-seq data sets are put together applying a poly-A purification step to enrich the mRNAs. This purification step reduces the possibility of identification of circRNAs that lack a poly-A tail (Kristensen et al, 2018)

Summary

Introduction

Cancer involves a broad range of dysregulations in the genome, transcriptome, and proteome. Another study by Zhong et al (2016) reported that the interaction of circTCF25 with miR-103a-3p/miR107 results in an upregulation of about 13 TFs playing role in cancer cell proliferation, migration, and invasion. An upregulation of circCCDC66 prevents the degradation of c-MYC mRNA via sponging miR-33b/miR-93 and resulting in the elevation of c-MYC levels and promotion of tumor cell growth and proliferation (Hsiao et al, 2017).

Results

Conclusion