Based on our investigation, lncRNA HCG11 regulates the expression level of SP1 by binding to the hsa-miR-106a-3p in a ceRNA axis. About the interaction of HCG11 and SP1 protein, Yin Duan et al. revealed that the up-regulation of HCG11 modulates the up-regulation of SP1 protein by decreasing the ubiquitination of SP1. Hence, in the TNBC cell line, this improved Sp1-mediated cell survival and invasion (29). There was no previous study about the ceRNA interaction of lncRNA HCG11 and SP1 in the BC patients.
About hsa-miR-106a-3p, Katharina Uhr et al. in 2019 revealed that miR-106a-3p is associated with the drug sensitivity in BC cell lines (30). The ceRNA LINC01133 suppresses the growth of gastric cancer via sponging miR-106a-3p to control APC production and the Wnt/-catenin pathway (31). Human vascular smooth muscle cells' exosome-mediated miR-106a-3p, which was produced by macrophages exposed to ox-LDL, increased cell proliferation and suppressed cell death (32). By targeting the SOCS System in gastric cancer, MicroRNA-106a-3p causes apatinib resistance and activates Janus-Activated Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) (33). circulating microRNAs from the chromosomal X miR-106a-363 cluster as fresh breast cancer diagnostic indicators (34). Also, based on the study of Zhang T et al. in 2021, ceRNA network and ROC analyses revealed that miR-106a-3p could be a key biomarker of Alzheimer’s disease (35).
Based on the study of Yan Zhang et al. in 2020, lncRNA HCG11 could inhibit the cervical cancer (CC) progression and invasion. Furthermore, proliferation factor-independent transcription repressor 1 (GFI1) was miR-942-target 5p's gene, and miR-942-5p suppression inhibited CC cell growth and invasion. HCG11, a long noncoding RNA that acts as a sponge for miR-942-5p, enhanced the expression of GFI1 and decreased cell invasion and proliferation. Finally, overexpression of the long noncoding RNA HCG11 inhibited the growth and metastasis of CC cells in vivo (36). In Non-Small-Cell Lung Cancer Cells (NSCLC), Lnc-HCG11 was considerably decreased. Lnc-HCG11 reduced NSCLC cell growth and brought on apoptosis. The NSCLC cell line has a considerably increased level of miR-224-3p. Additionally, miR-224-3p markedly accelerated cell division and prevented apoptosis in NSCLC cells. Additionally, there was a correlation between the expression of miR-224-3p and Lnc-HCG11. Caspase-3 and c-caspase-3 expression levels were up-regulated by the overexpression of lnc-HCG11 (37). The HCG11/miR-1276/CTNNB1 axis controlled the occurrence and progression of GC. Mouse tumor development demonstrated a positive association between HCG11 and CTNNB1 and a negative correlation between HCG11 and miR-1276 (38). The epithelial-to-mesenchymal transition is connected to the biochemical pathways seen for the HCG11 network, and it can be considered as a decoy for PUMILO proteins in the BC subtypes (39). In prostate cancer, the long noncoding RNA HCG11 targets miR-543 and controls the AKT/mTOR pathway to control cell growth (40). By altering miR-144-3p/PBX3 axis, lncRNA HCG11 knockdown slows the growth of ovarian cancer cells (41). lncRNA HCG11 controls the miR-942-5p/BRMS1 axis to act as a tumor suppressor in GC (42). By increasing SOCS5, the long non-coding RNA HCG11 sponging miR-522-3p prevents the growth of non-small cell lung cancer (43).
Based on our bioinformatics analyses, SP1 protein has significant interaction with EP300, MYC, and TP53 proteins. Based on the study of Mahmud Z et al. in 2019, by modifying FOXO3-acetylation and activity, EP300 and SIRT1/6 co-regulate lapatinib sensitivity in breast cancer (44). PARP1 co-regulates breast cancer cell proliferation and DNA repair-related genes through EP300-BRG1-dependent transcription (45). In triple-negative breast cancer, somatic EP300-G211S mutations are related to overall somatic mutational patterns and breast cancer-specific survival (46). In triple negative breast cancer, EP300 knockdown lessens the phenotypic, tumor size, and metastasis of cancer stem cells (47). About MYC, previous studies in 2021 revealed that circCD44 affects the miR-502-5p/KRAS and IGF2BP2/Myc axis in triple-negative breast cancer, which contributes to its oncogenic effects (48). By controlling the expression of the proto-oncogene MYC, circACTN4 collaborates with FUBP1 to advance the carcinogenesis and development of breast cancer (49). MYC expression varies among breast cancer subtypes, with TNBC expressing it the most frequently. As a transcription factor, MYC interacts with cancer stem cells in addition to taking part in the rewiring of cancer signaling pathways including estrogen, WNT, NOTCH, and other pathways. Breast cancer stem cell markers such CD44, CD24, and ALDH1 have a strong positive correlation with MYC (50). The majority of these target the p53/TP53 negative regulators, wtp53/TP53 (wild-type) and mtp53/TP53, to restore p53/TP53 function (mutant). Except for two compounds—APR-246 and COTI-2—that have advanced to clinical trials, the majority of these medicines are still in the preclinical stage (51).
Previous bioinformatics studies demonstrated that the systems biology approach reveals nove information about the molecular mechanism of different cancer types, like HCC (52) and BC (53, 54). However, it is highly recommended that the expression level of hsa-miR-106a-3p be evaluated by experimental methods (e.g., qRT-PCR) in the different populations of different cancer types, including BC. ROC analysis on the qRT-PCR expression data could be an excellent way to find the exact expression pattern of mentioned non-coding RNA regulating cancer development. Furthermore, the direct (physical) and indirect (ceRNA) interaction of SP1 and lncRNA HCG11 could be evaluated by RIP or luciferase assay methods, especially in interaction with hsa-miR-106a-3p.