|Table of Contents|

LncRNA IQCH-AS1 inhibits proliferation of progesterone-resistant endometrial carcinoma cells by regulating miR-494-3p/ARID1A axis

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 18
Page:
3335-3341
Research Field:
Publishing date:

Info

Title:
LncRNA IQCH-AS1 inhibits proliferation of progesterone-resistant endometrial carcinoma cells by regulating miR-494-3p/ARID1A axis
Author(s):
QIANG XianOUYANG JunWANG HaizhenGE Sumei
Department of Pathology,Changzhou Maternal and Child Health Care Hospital,Jiangsu Changzhou 213003,China.
Keywords:
LncRNA IQCH-AS1miR-494-3pARID1Aprogesteronedrug resistanceendometrial carcinoma
PACS:
R737.33
DOI:
10.3969/j.issn.1672-4992.2023.18.001
Abstract:
Objective:To investigate the impacts of LncRNA IQCH-AS1 on the proliferation and apoptosis of progesterone-resistant endometrial carcinoma (EC) cells by regulating miR-494-3p/ARID1A axis.Methods:Ishikawa cells were cultured in vitro and the EC progesterone resistant cell line Ishikawa/MPA was constructed.MTT method was applied to verify the drug resistance of Ishikawa/MPA cells.The expression of progesterone receptor (PR),LncRNA IQCH-AS1,miR-494-3p and ARID1A mRNA in Ishikawa cells and Ishikawa/MPA cells was detected by qRT-PCR.The double luciferase reporter gene experiment and RNA pull-down experiment were applied to verify the targeting relationship between LncRNA IQCH-AS1,miR-494-3p and ARID1A in Ishikawa/MPA cells.Ishikawa/MPA cells were grouped into Ad-NC group,Ad-IQCH-AS1 group,Ad-IQCH-AS1+miR-NC group and Ad-IQCH-AS1+miR-494-3p group.The expression of LncRNA IQCH-AS1,miR-494-3p,ARID1A mRNA and PR mRNA was detected by qRT-PCR.The cell proliferation activity was detected by MTT.The apoptosis rate was detected by flow cytometry.Western blot was applied to detect the expression of ARID1A,PR,CyclinD1,CDK4,cleaned-capase-3,and cleaned-PARP proteins.The effect of LncRNA IQCH-AS1 on the growth and MPA resistance of Ishikawa/MPA cells transplanted tumor in nude mice was observed by tumorigenesis experiment in nude mice.Results:The drug resistance index of Ishikawa/MPA cells constructed in this study was 4.33.The expression of PR mRNA,LncRNA IQCH-AS1 and ARID1A mRNA in Ishikawa/MPA cells was low,while the expression of miR-494-3p was high (P<0.05).It had been verified that miR-494-3p in Ishikawa/MPA cells had a targeted relationship with LncRNA IQCH-AS1 and ARID1A.Overexpression of LncRNA IQCH-AS1 in Ishikawa/MPA cells could down-regulate the expression of miR-494-3p,and up-regulate the expression of ARID1A,PR mRNA and protein,reduce the cell survival rate and the expression of CyclinD1,CDK4 proteins,and increase the cell apoptosis rate and the expression of cleaved-capase-3,cleaved-PARP proteins (P<0.05).The overexpression of miR-494-3p was able to attenuate the effect of overexpression of LncRNA IQCH-AS1 on the expression of ARID1A,PR,cell proliferation and apoptosis.In addition,overexpression of LncRNA IQCH-AS1 was able to inhibit the growth of transplanted tumor of Ishikawa/MPA cells in nude mice and reduce MPA resistance.Conclusion:LncRNA IQCH-AS1 regulates miR-494-3p/ARID1A axis to inhibit the proliferation of progesterone-resistant EC cells and induce their apoptosis.

References:

[1] SIEGEL RL,MILLER KD,WAGLE NS,et al.Cancer statistics,2023[J].CA Cancer J Clin,2023,73(1):17-48.
[2] SHETTY A,VENKATESH T,KABBEKODU SP,et al.LncRNA-miRNA-mRNA regulatory axes in endometrial cancer:a comprehensive overview[J].Arch Gynecol Obstet,2022,306(5):1431-1447.
[3] HAO C,LIN S,LIU P,et al.Potential serum metabolites and long-chain noncoding RNA biomarkers for endometrial cancer tissue[J].J Obstet Gynaecol Res,2023,49(2):725-743.
[4] FEI Y,LI Y,CHEN F.LncRNA-IQCH-AS1 sensitizes thyroid cancer cells to doxorubicin via modulating the miR-196a-5p/PPP2R1B signalling pathway[J].J Chemother,2022,16:1-9.
[5] YUAN L,FENG F,MAO Z,et al.Effects of erbuzhuyu decoction combined with acupuncture on endometrial receptivity are associated with the expression of miR-494-3p[J].Evid Based Complement Alternat Med,2020,2020:9739672.
[6] WANG H,TANG Z,LI T,et al.CRISPR/Cas9-mediated gene knockout of ARID1A promotes primary progesterone resistance by downregulating progesterone receptor B in endometrial cancer cells[J].Oncol Res,2019,27(9):1051-1060.
[7] DING F,QIU C,LI W,et al.CNR1 may reverse progesterone-resistance of endometrial cancer through the ERK pathway[J].Biochem Biophys Res Commun,2021,548:148-154.
[8] MA X,ZHAO T,YAN H,et al.Fatostatin reverses progesterone resistance by inhibiting the SREBP1-NF-κB pathway in endometrial carcinoma[J].Cell Death Dis,2021,12(6):544.
[9] MCDONALD ME,BENDER DP.Endometrial cancer:Obesity,genetics,and targeted agents[J].Obstet Gynecol Clin North Am,2019,46(1):89-105.
[10] 饶珺,陈金玲,冯元元,等.miR-647通过靶基因NLRC5调控子宫内膜癌细胞的增殖和凋亡[J].现代肿瘤医学,2022,30(17):3096-3101. RAO J,CHEN JL,FENG YY,et al.miR-647 regulates the proliferation and apoptosis of endometrial cancer cells through the target gene NLRC5[J].Modern Oncology,30(17):3096-3101.
[11] 王露露,吕巧英,罗雪珍.子宫内膜癌保育治疗孕激素耐药分子机制的相关研究进展[J].复旦学报:医学版,2021,48(3):410-417. WANG LL,LV QY,LUO XZ.Research progress on the molecular mechanisms involving in progesterone resistance of the fertility-sparing treatment in endometrial cancer[J].Fudan University Journal of Medical Sciences,2021,48(3):410-417.
[12] CHI S,LIU Y,ZHOU X,et al.Knockdown of long non-coding HOTAIR enhances the sensitivity to progesterone in endometrial cancer by epigenetic regulation of progesterone receptor isoform B[J].Cancer Chemother Pharmacol,2019,83(2):277-287.
[13] LI M,PENG J,SHI Y,et al.miR-92a promotes progesterone resistance in endometriosis through PTEN/AKT pathway[J].Life Sci,2020,242:117190.
[14] MA X,XIA M,WEI L,et al.ABX-1431 inhibits the development of endometrial adenocarcinoma and reverses progesterone resistance by targeting MGLL[J].Cell Death Dis,2022,13(12):1067.
[15] ZHU L,WANG X,WANG T,et al.miR-494-3p promotes the progression of endometrial cancer by regulating the PTEN/PI3K/AKT pathway[J].Mol Med Rep,2019,19(1):581-588.
[16] RESKE JJ,WILSON MR,HOLLADAY J,et al.Co-existing TP53 and ARID1A mutations promote aggressive endometrial tumorigenesis[J].PLoS Genet,2021,17(12):e1009986.
[17] MEGINO-LUQUE C,SISO P,MOTA-MARTORELL N,et al.ARID1A-deficient cells require HDAC6 for progression of endometrial carcinoma[J].Mol Oncol,2022,16(11):2235-2259.
[18] 丁菲,姜洁.姜黄素对子宫内膜癌孕激素抵抗的影响[J].山东大学学报(医学版),2021,59(4):35-41. DING F,JIANG J.Effects of curcumin on progesterone resistance in endometrial carcinoma[J].Journal of Shandong University (Health Science),2021,59(4):35-41.
[19] ASAKA S,LIU Y,YU ZC,et al.ARID1A regulates progesterone receptor expression in early endometrial endometrioid carcinoma pathogenesis[J].Mod Pathol,2023,36(2):100045.

Memo

Memo:
江苏省常州市卫生健康青苗人才培养(编号:CZQM2020102)
Last Update: 1900-01-01