ULM, a benign lesion present frequently in the muscular part of the uterine wall. The prevalence of their existence is increasing and still no proper therapeutics was found . Recently, various bioinformatics studies were applied to search the molecular mechanism of ULM disease. In the current in silico analysis, EGF, FYN, VCAN, TRIP13, FBXW7, GATA2, JAG1, TLR3, APOL1 were detected as DEGs expressed in samples with ULM disease.
EGF gene is found to be associated with the growth, development and differentiation of various types of cells. Takeshi Maruo et al. studies suggested EGF important role in regulating fibroid development. According to Jiayin Wang et al. observed the overexpression of EGF in cultured fibroid cells . Likewise, Johnston et al. revealed the dysfunctional role of EGF related signaling pathways in cancer. John Mendelsohn et al. also found EGF as target for cancer therapeutics . Thus, we infer that EGF gene may be a potent candidate of ULM by participating in various growth and development related signaling.
FYN gene belongs to tyrosine kinase family encodes protein that participates in cell growth, adhesion and immune response. Additionally, overexpression of this gene may pose negative impact in ULM cases .Khush R Mittal et al. also found that FYN gene upregulation leads to uterine fibroid . Moreover, Giulio Poli et al. showed FYN as target for many cancers .Ye-Gong Xie et al.showed that FYN gene upregulation promotes invading of cells and cell migration in breast carcinoma . Therefore, we speculate that FYN gene may be related with cell growth and adhesion and would prove to be one of the potential key of uterine fibroid for treatment.
VCAN being an important component of extracellular matrix (ECM) and involves in cell growth and motility. Reported work of Md Soriful Islam et al. revealed VCAN involvement in fibroid pathogenicity . John M. Norian MD et al. studies indicated VCAN variants in ECM rich uterine fibroid . Moreover, through our findings VCAN as involved in ECM interaction pathway may prove to be promising target of ULM.
TRIP13 gene encodes protein which shows thyroxine receptor interaction. Anna P. Ponnampalam et al. suggested the transcription factor TRIP13 dysfunction lead to endometriosis . Kenji Kurita et al. studies indicate TRIP13 important role in promoting colorectal carcinoma. According to S.Lu et al. overexpression of TRIP13 leads to human carcinoma . Though till now no studies could find overexpressed TRIP13 role in uterine leiomyoma hence, may prove to be novel target for treatment.
FBXW7 gene, a F box protein plays an important role in ubiquitin ligase mechanism.Cuevas et al.found FBXW7 gene involvement with uterine sarcomas at molecular level . Roland P. Kuiper et al. investigated that FBXW7 disruption lead to renal cell carcinoma . Since no studies till now indicate the role of FBXW7 in uterine leiomyoma. However, FBXW7 might be an attractive key for ULM by participating in ubiquitin mechanism.
GATA2 encodes protein involved in differentiation and proliferation in cells. Alan A. Arslan et al. indicates GATA2 underexpression in uterine fibroid . Cory A. Rubel et al. studies provided GATA2 transcript dysfunctional role in endometriosis . Feng-Ming Tien et al. suggested that GATA2 mutation may lead to acute myeloid lymphoma . Since, GATA2 was found through studies that its mutational effect leads to uterine leiomyoma so, may prove to be key target for fibrosis treatment.
JAG1 gene found to be as calcium binder and as growth factor. JAG1loss of function was studied in leiomyoma by Xiaoping Luo et al . According to Sandro Santagata et al. JAG1 expression was found to be related to prostrate carcinoma . Also, Jungwhoi Lee et al. through their work found JAG1 gene association with pancreatic carcinoma . Although, some studies revealed the association of JAG1 with uterine fibroid thus it may prove to be one of the candidate gene of uterine leiomyoma.
TLR3 gene activate innate immune response by producing cytokines. Svenja Allhorn et al. revealed through studies that TLR3 decreased expression in endometriosis . Bruno Salaun et al. investigated TLR3 activate apoptosis in human carcinoma . Francesca Bianchi et al. detected TLR3 as biomarker of lung carcinoma . However, till date no studies revealed TLR3 gene association with uterine fibroid thus would help in finding a novel candidate for Leiomyoma cases.
APOL1 plays role in lipid transport. Chien-An A. Hu et al. found that APOL1 overexpression leads to cell death in various carcinomas and kidney problems . Though no findings till date could associate APOL1 gene with Uterine Leiomyoma. Since, the present work suggests the APOL1 downregulation is closely related to Uterine Leiomyoma thus, may prove to be key target for Uterine Fibroid treatment.