HBx-MALAT-XB130通路对肝癌细胞生长和迁移的影响机制

目的探讨HBx-MALAT-XB130通路对肝癌细胞生长和迁移的影响机制。方法2019年6—10月于解放军联勤保障部队第962医院实验室进行实验,选取人肝癌细胞株,培养后分为低阻断组、中阻断组、高阻断组,分别加入r-分泌酶抑制剂(DAPT)1 ml、5 ml、10 ml处理。MTT法检测各组细胞生长能力,TUNEL法检测细胞凋亡情况,流式细胞仪检测细胞周期分布情况,使用Transwell小室实验检测细胞侵袭情况。结果培养24 h、48 h、72 h时人肝癌细胞生长率比较,低阻断组<中阻断组<高阻断组(F=15.683、24.658、28.667,P均<0.01),细胞凋亡率比较,低阻断组>中阻断组>高阻断组(F=16.856、22.337、18.697,P均<0.01);细胞侵袭和迁移能力比较,低阻断组<中阻断组<高阻断组(F=35.664、28.553,P均<0.01);于G1、S、G2期肝癌细胞比例比较,高阻断组>中阻断组>低阻断组(F=9.583、13.521、16.552,P均<0.01);Bcl-2相对表达量低阻断组>中阻断组>高阻断组,而Bax、Caspase3、p53相对表达量低阻断组<中阻断组<高阻断组(F=11.234、15.367、12.367、10.952,P均<0.01)。结论HBx-MALAT-XB130通路与肝癌细胞生长率、凋亡、侵袭、迁移和肝癌细胞的细胞同期分布情况有着密切的联系,能够为肝癌的临床治疗起到一定的参考作用。

XB130 inhibits healing of diabetic skin ulcers through the PI3K/Akt signalling pathway

BACKGROUND Diabetic skin ulcers,a significant global healthcare burden,are mainly caused by the inhibition of cell proliferation and impaired angiogenesis.XB130 is an adaptor protein that regulates cell proliferation and migration.However,the role of XB130 in the development of diabetic skin ulcers remains unclear.AIM To investigate whether XB130 can regulate the inhibition of proliferation and vascular damage induced by high glucose.Additionally,we aim to determine whether XB130 is involved in the healing process of diabetic skin ulcers,along with its molecular mechanisms.METHODS We conducted RNA-sequencing analysis to identify the key genes involved in diabetic skin ulcers.We investigated the effects of XB130 on wound healing using histological analyses.In addition,we used reverse transcription-quantitative polymerase chain reaction,Western blot,terminal deoxynucleotidyl transferasemediated dUTP nick end labeling staining,immunofluorescence,wound healing,and tubule formation experiments to investigate their effects on cellular processes in human umbilical vein endothelial cells(HUVECs)stimulated with high glucose.Finally,we performed functional analysis to elucidate the molecular mechanisms underlying diabetic skin ulcers.RESULTS RNA-sequencing analysis showed that the expression of XB130 was up-regulated in the tissues of diabetic skin ulcers.Knockdown of XB130 promoted the healing of skin wounds in mice,leading to an accelerated wound healing process and shortened wound healing time.At the cellular level,knockdown of XB130 alleviated high glucose-induced inhibition of cell proliferation and angiogenic impairment in HUVECs.Inhibition of the PI3K/Akt pathway removed the proliferative effects and endothelial protection mediated by XB130.CONCLUSION The findings of this study indicated that the expression of XB130 is up-regulated in high glucose-stimulated diabetic skin ulcers and HUVECs.Knockdown of XB130 promotes cell proliferation and angiogenesis via the PI3K/Akt signalling pathway,which accelerates the healing of diabetic skin ulcers.