CircLRP6调节miR-125a-5p/MCL1轴对食管鳞癌顺铂耐药性的影响  

Impacts of circLRP6 on cisplatin resistance to esophageal squamous cell carcinoma by regulating miR⁃125a⁃5p/MCL1 axis

作　　者：林萍萍[1] 李富博[1] 王东娟[1] 郭研 董怡 LIN Pingping;LI Fubo;WANG Dongjuan;GUO Yan;DONG Yi(Department of Oncology,Affiliated Hospital of Chengde Medical College,Chengde 067000,China)

机构地区：[1]承德医学院附属医院肿瘤科,河北承德067000

出　　处：《实用医学杂志》2023年第17期2183-2189,共7页The Journal of Practical Medicine

基　　金：河北省自然科学基金(编号:H2021406013)。

摘　　要：目的探讨环状RNA脂蛋白受体6(circLRP6)对食管鳞癌(ESCC)顺铂(CDDP)耐药性的影响及潜在分子机制。方法建立KYSE30的CDDP抗性细胞株(KYSE30/CDDP-R),分为对照(Control)组、si-NC组、si-circLRP6组、si-circLRP6+anti-NC组、si-circLRP6+anti-miR-125a-5p组。采用RT-qPCR和Western blot检测组织/细胞中circLRP6、miR-125a-5p和髓样细胞白血病-1(MCL-1)的表达水平;CCK-8法检测KYSE30/CDDP-R细胞的CDDP敏感性;流式细胞术检测细胞凋亡。结果ESCC癌组织/细胞和CDDP耐药癌组织中circLRP6、MCL-1 mRNA水平升高,miR-125a-5p水平降低(P<0.001);circLRP6沉默可上调miR-125a-5p,抑制MCL-1表达,增强体内外CDDP抗性ESCC细胞对CDDP的敏感性,促进CDDP抗性ESCC细胞凋亡;抑制miR-125a-5p可减弱circLRP6沉默对CDDP抗性ESCC细胞中CDDP耐药性和细胞凋亡的影响。circLRP6可靶向负调控miR-125a-5p表达,MCL-1是miR-125a-5p的靶标。结论circLRP6沉默可能通过miR-125a-5p/MCL-1轴增强CDDP抗性ESCC细胞对CDDP的敏感性。Objective To investigate the impacts of circular RNA lipoprotein receptor 6(circLRP6)on cisplatin(CDDP)resistance to esophageal squamous cell carcinoma(ESCC)and its relevant potential molecular mechanism.Methods CDDP⁃resistant cell lines of KYSE30(KYSE30/CDDP⁃R)were established and divided into a control group,si⁃NC group,si⁃circLRP6 group,si⁃circLRP6 plus anti⁃NC group,and si⁃circLRP6 plus anti⁃miR⁃125a⁃5p group.The expression levels of circLRP6,miR⁃125a⁃5p and myeloid leukemia⁃1(MCL⁃1)in tissues/cells were detected by RT⁃qPCR and Western blot.CCK⁃8 assay was applied to detect the CDDP sensitivity of KYSE30/CDDP⁃R cells,so was flow cytometry to detect apoptosis.Results mRNA levels of circLRP6 and MCL⁃1 were increased,while level of miR⁃125a⁃5p was decreased in ESCC cancer tissues/cells and CDDP⁃resistant cancer tissues(P<0.001).CircLRP6 silencing was able to up⁃regulate miR⁃125a⁃5p,inhibit the expression of MCL⁃1,enhance the sensitivity of CDDP⁃resistant ESCC cells to CDDP in vitro and in vivo,and promote the apoptosis of CDDP⁃resis⁃tant ESCC cells.Inhibition of miR⁃125a⁃5p weakened the effects of circLRP6 silencing on CDDP resistance and apoptosis in CDDP⁃resistant ESCC cells(P<0.05).circLRP6 could target and negatively regulate the expression of miR⁃125a⁃5p,and MCL⁃1 was the target of miR⁃125a⁃5p.Conclusion CircLRP6 silencing may enhance the sensi⁃tivity of CDDP⁃resistant ESCC cells to CDDP through the miR⁃125a⁃5p/MCL⁃1 axis.

关 键 词：环状RNA脂蛋白受体6 食管鳞癌 顺铂耐药 miR-125a-5p/MCL-1轴 

分 类 号：R735.1[医药卫生—肿瘤]