Identification of miR‐3182 and miR‐3143 target genes involved in the cell cycle as a novel approach in TNBC treatment: A systems biology approach

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, lacking therapeutic targets. miRNAs play crucial roles in TNBC through regulating various mechanisms, including cellular growth and proliferation. This study aims to identify critical target genes of two novel miRNAs (miR-3143 and miR-3182) involved in the cell cycle of TNBC as possible therapeutic targets and investigates their regulatory and therapeutic roles through a systems biology approach and in vitro experiment. Datasets related to the TNBC cell line (MDA-MB-231) were screened and retrieved, and Gene regulatory networks were constructed. Significant regulatory motifs were detected and analyzed using the FANMOD and Cytoscape analyzer, and the clusters and seeds were identified using the MCODE. Functional enrichment analysis was also performed using DAVID and STRING. The most critical genes were determined using the analysis of GRN motifs and PPI clusters. The essential genes involved in the cell cycle were selected and verified using the bc-GenExMiner v4.7. We overexpressed miR-3143 and miR-3182 in the MDA-MB-231 cell line using human umbilical cord mesenchymal stem cell (HUCMSC)-miRNA loaded exosomes, and the expression of the critical target genes was investigated using RT-qPCR. We identified eight critical genes as potential therapeutic targets. Their expression decreased by overexpression of miR-3143 and miR-3182 in RT-qPCR.The identified critical genes have probably significant roles in the pathogenesis of TNBC through the cell cycle. We suggest that the overexpression of miR-3143

miRNA-Guided Regulation of Mesenchymal Stem Cells Derived from the Umbilical Cord: Paving the Way for Stem-Cell Based Regeneration and Therapy

“…UCMSC-derived exosomes transfected with miR-21-5p were shown to possess tumor-suppressing properties in the case of breast cancer cells by directly targeting ZNF367 and suppressing its migration and invasion properties [194]. Similarly, UCMSC-exosomes modified to overexpress miR-148b-3p were found to inhibit tumor formation and the process of EMT in mice by blocking the oncogenic properties of breast cancer cells and promoting their apoptosis [195], while two more novel anti-oncogenic microRNAs, miR-3182 and miR-3143, were identified as rather promising candidates for the exosome-based therapy of triple negative cancer, with their targets revealed as key genes in cancer pathogenesis [196,197]. On the other hand, miR-224-5p was found highly upregulated in both breast cancer cells and tissues, promoting the autophagic and the oncogenic activity of breast cancer cells by targeting HOXA5 [198].…”

Comprehensive analysis of lncRNA‐associated ceRNA network reveals novel potential prognostic regulatory axes in glioblastoma multiforme

“…Several research studies have used different systems biology approaches, including protein–protein interaction (PPI) network analysis and gene regulatory networks (GRNs), to decipher the molecular pathology behind various illnesses and conditions. 5 , 6 , 7 , 8 Some research has stated that GRN disruption is related to developing various diseases, including GBM. 9 , 10 Besides, studies have demonstrated a role for both protein‐coding and non‐coding RNAs (ncRNA) in aberrant gene expression and GBM progression 11 , 12 , 13 ; However, their regulatory relationships and functions are still largely unknown.…”

“…Several research studies have used different systems biology approaches, including protein–protein interaction (PPI) network analysis and gene regulatory networks (GRNs), to decipher the molecular pathology behind various illnesses and conditions 5–8 . Some research has stated that GRN disruption is related to developing various diseases, including GBM 9,10 .…”

In Silico Study of a Small Bioactive Molecule Targeting Topoisomerase II and P53-MDM2 Complex in Triple-Negative Breast Cancer

“…Breast cancer is one of the leading causes of death globally owing to its diversity and rapid rate of mutations that lead to change in its characteristics very fast; thus, in several cases common therapeutics could not produce desired outcomes. About 10–15% of all breast cancers are called triple-negative breast cancers (TNBCs) as this breast cancer subtype does not have progesterone and estrogen hormone receptors (PR or ER), and HER2 overexpression too. − This type of cancer cell is generally aggressive as it grows more rapidly. It would be worth mentioning here that only few systemic treatment options are available along with chemotherapy (CT) to treat the TNBCs. − The ‘single drug and single target’ approach does not provide great success.…”

“…About 10–15% of all breast cancers are called triple-negative breast cancers (TNBCs) as this breast cancer subtype does not have progesterone and estrogen hormone receptors (PR or ER), and HER2 overexpression too. − This type of cancer cell is generally aggressive as it grows more rapidly. It would be worth mentioning here that only few systemic treatment options are available along with chemotherapy (CT) to treat the TNBCs. − The ‘single drug and single target’ approach does not provide great success. Moreover, eradication of the resistant cancer cells is a major challenge, where multitarget therapeutics might offer better option as it concurrently inhibits several cellular pathways and thus becomes more lethal toward cancer cells.…”