Functional role of circular RNAs in cancer development and progression

Abstract

Circular RNAs (circRNAs) are a large class of endogenously expressed non-coding RNAs formed by covalently closed loops through back-splicing. High throughput sequencing technologies have identified thousands of circRNAs with high sequence conservation and cell type specific expression in eukaryotes. CircRNAs play multiple important roles in cellular physiology functioning as miRNA sponges, transcriptional regulators, RBP binding molecules, templates for protein translation, and immune regulators. In a clinical context, circRNAs expression is correlated with patient's clinicopathological features in cancers including breast, liver, gastric, colorectal, and lung cancer. Additionally, distinct properties of circRNAs, such as high stability, exonuclease resistance, and existence in body fluids, show promising role for circRNAs as molecular biomarkers for tumor diagnosis, non-invasive monitoring, prognosis, and therapeutic intervention. Therefore, it is critical to further understand the molecular mechanism underlying circRNAs interaction in tumors and the recent progress of this RNA species in cancer development. In this review, we provide a detailed description of biological functions, molecular role of circRNAs in different cancers, and its potential role as biomarkers in a clinical context.

The circRNA circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer

“…In recent years, the role of circRNAs in oncogenesis and cancer progression has caused wide attention. Due to cell/tissue-specific and stage-specific expression and unique molecular structure, circRNAs might have regulatory functions in many biological processes and are better diagnostic markers or therapeutic targets for cancer than linear transcripts [23]. However, the expression and role of most circRNAs in TNBC development are still largely unclear.…”

<p>Circular RNA hsa_circ_0068033 Acts as a Diagnostic Biomarker and Suppresses the Progression of Breast Cancer Through Sponging miR-659</p>

“…4,5,8,13,18,19 Recent studies have confirmed that circRNA is involved in the regulation of gene expression by various means, thereby indirectly participating in the occurrence and development of various solid cancers. 6,[9][10][11]13,14,16,17 However, the biological functions of circRNA in BC are scarcely reported. In this study, we investigated the expression of hsa_circ_0068033 expression in BC tissues and cell lines and explored the influence of overexpressed hsa_circ_0068033 on the biological characteristics of MCF-7 and MDA-MB-231.…”

“…6,7 In addition, circRNA can directly bind to proteins, or establish an indirect RNA-mediated association with proteins to influence their functions. 8 Studies have reported that circRNA is closely correlated with the occurrence and development of various malignant tumors, including liver cancer, 9,10 lung cancer, 11,12 cervical cancer 13 gastric cancer, 14,15 colorectal cancer, 16,17 etc. In recent years, the potential applications of circRNA in the regulation of biological functions and the clinical diagnosis and prognosis of BC have received considerable attention.…”

Circular RNA hsa_circ_0068033 inhibits proliferation and invasion of breast cancer cells through sponging miR-659

“…CircRNA, a class of enclosed non-coding RNA molecules generated by RNA splicing, function as an miRNA sponge and regulate gene transcription and alternative splicing [18,19,8,13,4,5]. Recent studies have confirmed that circRNA is involved in the regulation of gene expression by various means, thereby indirectly participating in the occurrence and development of various solid cancers [13,11,10,6,17,9,16,14].…”

“…In addition, circRNA can directly bind to proteins, or establish an indirect RNA-mediated association with proteins to influence their functions [8]. Studies have reported that circRNA is closely correlated with the occurrence and development of various malignant tumors, including liver cancer [9,10], lung cancer [11,12], cervical cancer [13] gastric cancer [14,15], colorectal cancer [16,17], etc. In recent years, the potential applications of circRNA in the regulation of biological functions and the clinical diagnosis and prognosis of BC have received considerable attention.…”