Circular RNA hsa_circ_0044234 as distinct molecular signature of triple negative breast cancer: a potential regulator of GATA3

Abstract

Background Circular RNAs (circRNAs) have been implicated in the initiation and development of breast cancer as functional non-coding RNAs (ncRNA). The roles of circRNAs as the competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) have also been indicated. However, the functions of circRNAs in breast cancer have not been totally elucidated. This study aimed to explore the clinical implications and possible roles of circ_0044234 in carcinogenesis of the most problematic BC subtype, triple negative breast cancer (TNBC), which are in desperate need of biomarkers and targeted therapies. Methods The importance of circ_0044234 as one of the most dysregulated circRNAs in TNBC was discovered through microarray expression profile analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the downregulation of circ_0044234 in triple negative tumors and cell lines versus non-triple negative ones. The bioinformatics prediction revealed that circ_0044234 could act as an upstream sponge in the miR-135b/GATA3 axis, two of the most dysregulated transcripts in TNBC. Results Our experimental investigation of circ_0044234 expressions in various BC subtypes as well as cell lines reveals that TNBC expresses circ_0044234 at a substantially lower level than non-TNBC. The ROC curve analysis indicates that it could be applied as a discriminative biomarker to identify TNBC from other BC subtypes. Moreover, circ_0044234 expression could be an independent prognostic biomarker in BC. Interestingly, a substantial inverse expression correlation was detected between circ_0044234 and miR-135b-5p as well as between miR-135b-5p and GATA3 in breast tumors. Conclusions The possible clinical usefulness of circ_0044234 as a promising distinct biomarker and upcoming therapeutic target for TNBC have been indicated in this research. Our comprehensive approach revealed the potential circ_0044234/miR135b-5p/GATA3 ceRNA axis in TNBC.

Hsa_circ_0001925 promotes malignant progression in triple‐negative breast cancer via miR‐1299/YY1 axis

“…19 Circ_0044234 could be used as a biomarker to distinguish TNBC from other BC subtypes and inhibit the development of TNBC via the circ_0044234/ miR135b-5p/GATA3 axis. 20 Moreover, knockdown of cir-cUBE2D2 inhibited cell proliferation and metastasis and reduced the resistance of TNBC cells to adriamycin. 21 Previous studies revealed that the level of hsa_circ_0001925 was elevated in BC tissues compared with that in adjacent normal tissues.…”

“…For example, circPDCD11 accelerated aerobic glycolysis by accelerating ATP production, glucose uptake, lactate production and extracellular acidification rate of TNBC cells 19 . Circ_0044234 could be used as a biomarker to distinguish TNBC from other BC subtypes and inhibit the development of TNBC via the circ_0044234/miR135b‐5p/GATA3 axis 20 . Moreover, knockdown of circUBE2D2 inhibited cell proliferation and metastasis and reduced the resistance of TNBC cells to adriamycin 21 .…”

Circular RNAs in and out of Cells: Therapeutic Usages of Circular RNAs

“…The lesions of patients with various types of cancers, neurological diseases, retinal diseases, and diabetes all have been shown to have significant changes in circular RNA expression ( Hanineva et al, 2022 ; Lei et al, 2020 ; Li et al, 2021 ; Sakshi et al, 2021 ; Sun et al, 2020 ). For example, circ_0044234, a circular RNA that was found to be significantly downregulated in triple-negative breast cancer (TNBC) compared to other breast cancer types was suggested to be a promising biomarker for the diagnosis of TNBC ( Darbeheshti et al, 2021 ).…”

Investigation of BRCAness associated miRNA-gene axes in breast cancer: cell-free miR-182-5p as a potential expression signature of BRCAness

“…However, it is well known that epigenetic mechanisms could change protein expression without any changes in DNA sequences [ 15 , 16 ]. RNA interference, as an epigenetic mechanism, has prominent roles in the dysregulation of gene expression profile in tumor cells [ 17 , 18 ].…”