A New World of Biomarkers and Therapeutics for Female Reproductive System and Breast Cancers: Circular RNAs

Abstract

As one of the most recently (re)discovered types of non-coding RNAs (ncRNA), circular RNAs (circRNAs) differentiate from other ncRNAs by a specific biogenesis, high stability, and distinct functions. The biogenesis of circRNAs can be categorized into three mechanisms that permit the back-splicing reaction: exon-skipping, pairing of neighboring introns, and dimerization of RNA-binding proteins. Regarding their stability, circRNAs have no free ends, specific to linear RNA molecules, prompting a longer half-life and resistance to exonuclease-mediated activity by RNase R, bypassing the common RNA turnover process. Regarding their functions, circular transcripts can be categorized into four broad roles: miRNA sponging, protein binding, regulation of transcription, and coding for proteins and peptides. Female reproductive system (including mainly ovarian, corpus, and cervix uteri cancers) and breast cancers are the primary causes of death in women worldwide, accounting for over 1,212,772 deaths in 2018. We consider that a better understanding of the molecular pathophysiology through the study of coding and non-coding RNA regulators could improve the diagnosis and therapeutics of these cancers. Developments in the field of circRNA in regard to breast or gynecological cancers are recent, with most circRNA-related discoveries having been made in the last 2 years. Therefore, in this review we summarize the newly detected roles of circRNAs in female reproductive system (cervical cancer, ovarian cancer, and endometrial cancer) and breast cancers. We argue that circRNAs can become essential elements of the diagnostic and therapeutic tools for female reproductive system cancers in the future.

<p>Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer</p>

“…Cervical cancer, as one of the common human tumors, is one of the most common gynecological malignancies, [1][2][3][4][5]34 which is like other tumors [35][36][37][38][39][40][41] and they threatened seriously to human health as well as cervical cancer, [42][43][44][45][46][47][48] its morbidity and mortality rate are at the forefront of female malignancies. Surgery, radiotherapy and chemotherapy for early cervical cancer have good effects, but in advanced stage, the therapeutic effect of metastatic and recurrent cervical cancer is very limited and the survival rate is low.…”

“…Cervical cancer is considered to be one of the most common gynecological malignant tumors in the world and highly occurred in developing countries, [1][2][3][4][5] which is a serious threat to women's health. Globally, cervical cancers rank the fourth one among female tumor causes of death and the incidence of cervical cancer ranks the first one among female genital malignancies in China.…”

Identification and Characterization of Circular RNA as a Novel Regulator and Biomarker in Preterm Birth

“…Eleven of these 20 circRNAs have never been reported before, and we speculated that their dysregulation might be specific for PTB. The remaining 9 circRNAs have been demonstrated to be correlated with breast cancer (hsa-SCARF1_0001), osteoarthritis (hsa-GCN1_0003), osteosarcoma (hsa-RAD54L2_002), virus infection (hsa-CREBBP_0001), ovarian cancer (hsa-FAM13B_0019), hepatocellular carcinoma (hsa-NUSAP1_0010), endometrial cancer (hsa-YY1AP1_0001), hypopharyngeal squamous cell carcinoma (hsa-MORC3_0001), and gestational diabetes mellitus (hsa-RANBP9_0002) (Fu et al, 2018;Kun-Peng et al, 2018;Hu et al, 2019;Li et al, 2019;Lou et al, 2019;Wang et al, 2019Wang et al, , 2020Guo et al, 2020;Tran et al, 2020). Interestingly, we found that all these diseases shared a common pathological ground of inflammation and immune activation with PTB, which happens to be the main way that the selected circRNAs regulate these diseases (Cappelletti et al, 2016).…”

Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR‐326/FGFR1 axis

“…20 Some cir-cRNAs have been verified as latent therapeutic targets and novel biomarkers in a series of diseases, including tumors. 21 A previous report revealed that circRNA circ_KDM4C moderated doxorubicin resistance and impeded tumor growth in BC through increasing PBLD expression by sponging miR-548p. 22 Also, circRNA hsa_circ_0009362, 23 circRNA circ_TFF1, 24 and circRNA circ_circACAP2 25 contributed to the advancement of BC.…”