Mechanistic Analysis Of Endothelial Lipase G Promotion Of The Occurrence And Development Of Cervical Carcinoma Via Activating The PI3k/Akt/mTOR Signaling Pathway

ObjectiveLipase G,endothelial type(LIPG)is a phospholipase that is mainly situated in the cell membrane and cytoplasm.It is abundantly expressed in tissues with a high metabolic rate and vascularization,thereby providing lipid precursors,such as ATP,fatty acids,lipids,and nucleotides,which can maintain cell energy for rapid growth,proliferation,migration,and apoptosis.Research on LIPG has focused on metabolic syndromes,such as atherosclerosis,cardiovascular disease,and inflammation.However,the role of LIPG in providing lipid precursors for cells suggests that it might act a fundamental part in the metabolism of carcinoma cells,such as cell proliferation,angiogenesis and energy supply.LIPG was regarded to be highly expressed and to support proliferation,tumor sensitization,metastasis in breast carcinoma.However,the underlying mechanism of LIPG in cervical carcinoma is unclear.The original intention of the present study was to detected whether LIPG participates in the occurrence and development of cervical carcinoma.Methods1.Immunohistochemistry was utilized to evaluate the expression of LIPG in normal cervical(n=19)and cervical carcinoma tissues(n=81).2.Quantitative real-time reverse transcription polymerase chain reaction(q RT-PCR)was used to test the expression of LIPG in cervical cancer cells,tissue specimens(normal cervical tissue:n=30,cervical cancer tissues: n=87),and to figure out the transfection efficiency of LIPG small interfering RNAs(siRNAs),and to verify its relationship with HPV16 E6 and miR-148a-3p.3.Western blotting was carried out to determine alterations in the levels of protein.These techniques were used to clarify the relationship between HPV16E6 and LIPG,and to verify its potential role in the phosphatidylinositol-4,5-bisphosphate3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin kinase(mTOR)signaling pathway.4.Dual luciferase reporter system was executed to detect the connection between miR-148a-3p and LIPG.5.Cell migration was assessed using a wound healing assessment.6.Cell proliferation was examined using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide appraisal.7.To understand unknown effect of LIPG on apoptosis,flow cytometry was used.8.Invasion experiments were executed to validate the function of LIPG in carcinoma cell invasion.Results1.The results of immunohistochemistry,western blotting and q RT-PCR signified that LIPG was expressed in cervical carcinoma,and its expression level was higher in cervical cancer than in normal cervical tissue.2.Downregulation of LIPG expression inhibited cell migration,invasion,proliferation,and the formation of cell colonies,but increased the rate of apoptosis.3.In addition,the results indicated that LIPG might be regulated by HPV16E6/miR-148a-3p,and could promote cervical carcinoma progression via the PI3K/AKT/mTOR signaling pathway.ConclusionsAfter cervical infection with HPV virus,HPV E6 protein may reduce the expression of miR-148a-3p,relieve the inhibitory effect of miR-148a-3p on LIPG expression,and promote the progression of cervical cancer through the PI3k/Akt/mTOR signaling pathway.