Investigating isoform switching in RHBDF2 and its role in neoplastic growth in breast cancer

Abstract

Background Breast cancer is the second leading cause of cancer-related deaths globally, and its prevalence rates are increasing daily. In the past, studies predicting therapeutic drug targets for cancer therapy focused on the assumption that one gene is responsible for producing one protein. Therefore, there is always an immense need to find promising and novel anti-cancer drug targets. Furthermore, proteases have an integral role in cell proliferation and growth because the proteolysis mechanism is an irreversible process that aids in regulating cellular growth during tumorigenesis. Therefore, an inactive rhomboid protease known as iRhom2 encoded by the gene RHBDF2 can be considered an important target for cancer treatment. Speculatively, previous studies on gene expression analysis of RHBDF2 showed heterogenous behaviour during tumorigenesis. Consistent with this, several studies have reported the antagonistic role of iRhom2 in tumorigenesis, i.e., either they are involved in negative regulation of EGFR ligands via the ERAD pathway or positively regulate EGFR ligands via the EGFR signalling pathway. Additionally, different opinions suggest iRhom2 mediated cleavage of EGFR ligands takes place TACE dependently or TACE independently. However, reconciling these seemingly opposing roles is still unclear and might be attributed to more than one transcript isoform of iRhom2. Methods To observe the differences at isoform resolution, the current strategy identified isoform switching in RHBDF2 via differential transcript usage using RNA-seq data during breast cancer initiation and progression. Furthermore, interacting partners were found via correlation and enriched to explain their antagonistic role. Results Isoform switching was observed at DCIS, grade 2 and grade 3, from canonical to the cub isoform. Neither EGFR nor ERAD was found enriched. However, pathways leading to TACE-dependent EGFR signalling pathways were more observant, specifically MAPK signalling pathways, GPCR signalling pathways, and toll-like receptor pathways. Nevertheless, it was noteworthy that during CTCs, the cub isoform switches back to the canonical isoform, and the proteasomal degradation pathway and cytoplasmic ribosomal protein pathways were significantly enriched. Therefore, it could be inferred that cub isoform functions during cancer initiation in EGFR signalling. In contrast, during metastasis, where invasion is the primary task, the isoform switches back to the canonical isoform.

Adaptive Sparse Multi-Block PLS Discriminant Analysis: An Integrative Method for Identifying Key Biomarkers from Multi-Omics Data

“…Among the other four genes selected by asmbPLS-DA, STOM, MMGT1, and DIAPH3 are associated with breast cancer progression [39][40][41], while FAM72B is related to lung adenocarcinoma [42]. In contrast, sPLS-DA selected RHBDF2 and CCL14 related to breast cancer [43,44], while ERG and FASTKD1 are associated with other cancers [45,46]. The associations between the genes selected by L1-regularized multinomial logistic regression and breast cancer are not supported by the available literature.…”

Topical Agents Used by Housewives as First Aid Burns in Sleman District Yogyakarta Indonesia

“…Providing the right first aid in the event of a burn can increase the outcome in the event of a burn (Graham, H.E., et al, 2012). Management of topical agents that can be given to burns is an agent containing silver/silver sulfadiazine (Masood et al, 2018).…”

“…A study conducted in developing countries, there are also people were used raw eggs (12, 5%), water lavage (29, 2%), pap in (9, 5%) and other ingredients (48, 8%) (Fadeyibi, I.O., et al, 2015). In addition, there are also those who use honey, a mixture of gum and goat hair, and tanic acid spray (Masood et al, 2018). Until now, not all traditional topical agents have been scientifically validated about the benefits and safety to be given in burn cases.…”