LncRNA SNHG11通过抑制miR-184/CARM1信号轴促进卵巢癌生长

doi:10.11958/20221256

天津医药 ›› 2023, Vol. 51 ›› Issue (6): 561-567.doi: 10.11958/20221256

• 细胞与分子生物学 • 下一篇

LncRNA SNHG11通过抑制miR-184/CARM1信号轴促进卵巢癌生长

李少儒¹(), 李燕², 刘珊¹, 户瑞丽¹

1 新乡医学院第一附属医院妇科（邮编453100）
2 新乡医学院第一附属医院内分泌科（邮编453100）

收稿日期:2022-08-11 修回日期:2022-10-14 出版日期:2023-06-15 发布日期:2023-06-20
作者简介:李少儒（1983），男，副主任医师，主要从事妇科与妇科肿瘤方面研究。E-mail：qmfm40@163.com
基金资助:
河南省医学科技攻关计划联合共建项目(LHGJ20200525)

Influences of lncRNA SNHG11 on proliferation, apoptosis, migration and invasion of ovarian cancer cells by regulating miR-184/CARM1 signaling axis

LI Shaoru¹(), LI Yan², LIU Shan¹, HU Ruili¹

1 Department of Gynecology, the First Affiliated Hospital of Xinxiang Medical College, Xinxiang 453100, China
2 Department of Endocrine, the First Affiliated Hospital of Xinxiang Medical College, Xinxiang 453100, China

Received:2022-08-11 Revised:2022-10-14 Published:2023-06-15 Online:2023-06-20

李少儒, 李燕, 刘珊, 户瑞丽. LncRNA SNHG11通过抑制miR-184/CARM1信号轴促进卵巢癌生长[J]. 天津医药, 2023, 51(6): 561-567.

LI Shaoru, LI Yan, LIU Shan, HU Ruili. Influences of lncRNA SNHG11 on proliferation, apoptosis, migration and invasion of ovarian cancer cells by regulating miR-184/CARM1 signaling axis[J]. Tianjin Medical Journal, 2023, 51(6): 561-567.

摘要/Abstract

摘要：

目的探讨长链非编码RNA核仁小分子RNA宿主基因11（LncRNA SNHG11）靶向调控miR-184/CARM1信号轴对卵巢癌细胞的影响及其机制。方法实时荧光定量PCR检测卵巢癌组织与细胞中LncRNA SNHG11表达及卵巢癌细胞miR-184表达。将卵巢癌SKOV3细胞分为si-NC组、si-SNHG11组、si-SNHG11+anti-NC组、si-SNHG11+anti-miR-184组、miR-NC组、miR-184 mimics组、miR-184 mimics+pcDNA组、miR-184 mimics+CARM1组，分别检测各组细胞增殖、凋亡、迁移、侵袭及CARM1、E-cadherin、N-cadherin蛋白表达，裸鼠成瘤实验检测各组细胞在动物体内成瘤能力，双荧光素酶报告基因实验检验miR-184与LncRNA SNHG11、CARM1的靶向关系。结果 LncRNA SNHG11在卵巢癌组织与细胞中表达升高，miR-184在卵巢癌细胞中表达降低（P<0.05）。与si-NC组比较，si-SNHG11组SKOV3细胞增殖、迁移与侵袭能力下降，瘤体质量与体积减小，N-cadherin表达降低，细胞凋亡率与E-cadherin蛋白表达升高（P<0.05）；与si-SNHG11+anti-NC组比较，si-SNHG11+anti-miR-184组SKOV3细胞增殖、迁移与侵袭细胞能力升高，瘤体质量与体积增大，N-cadherin蛋白表达升高，细胞凋亡率与E-cadherin蛋白表达降低（P<0.05）。与miR-NC组比较，miR-184 mimics组SKOV3细胞增殖、迁移与侵袭能力下降，瘤体质量与体积减小，N-cadherin蛋白表达降低，细胞凋亡率与E-cadherin蛋白表达升高（P<0.05）；与miR-184 mimics+pcDNA组比较，miR-184mimics+CARM1组SKOV3细胞增殖、迁移与侵袭能力升高，瘤体质量与体积增大，N-cadherin蛋白表达升高，细胞凋亡率与E-cadherin蛋白表达降低（P<0.05）；LncRNA SNHG11靶向调控miR-184/CARM1信号轴。结论 LncRNA SNHG11通过调节miR-184/CARM1信号轴，促进卵巢癌生长。

关键词: 卵巢肿瘤, 肿瘤浸润, 基因治疗, 长链非编码RNA核仁小分子RNA宿主基因11, 微小RNA-184, 共激活相关精氨酸甲基转移酶1

Abstract:

Objective To investigate the effect of long chain non coding RNA nucleolar small RNA host gene 11 (lncRNA SNHG11) targeting miR-184/CARM1 signal axis on ovarian cancer cells and its mechanism. Methods Expression levels of lncRNA SNHG11 and miR-184 in ovarian cancer tissue and cells were detected by real time fluorescent quantitative PCR (qPCR), and SKOV3 cells were selected for the experiment. SKOV3 cells were divided into the si-NC group (transfected with si-NC), the si-SNHG11 group (transfected with si-SNHG11), the si-SNHG11+anti-NC group (transfected with si-SNHG11+anti-NC), the si-SNHG11+anti-miR-184 group (transfected with si-SNHG11+anti-miR-184), the miR-NC group (transfected with miR-NC), the miR-184 mimics group (transfected with miR-184 mimics), the miR-184 mimics+pcDNA group (transfected with miR-184 mimics+pcDNA) and the miR-184 mimics+CARM1 group (transfected with miR-184 mimics+pcDNA-CARM1). The cell proliferation, apoptosis, migration, invasion and the expression levels of CARM1, E-cadherin, N-cadherin protein in each group were detected respectively. The tumorigenicity of each group of cells in vivo was detected by nude mouse tumorigenesis experiment. The targeting relationship between miR-184 and lncRNA SNHG11, CARM1 was detected by double luciferase reporter gene experiment. Results The expression level of lncRNA SNHG11 was increased in ovarian cancer tissue and cells, and the expression level of miR-184 was decreased in ovarian cancer cells (P<0.05). Compared with the si-NC group, the proliferation, migration and invasion ability of SKOV3 cells were decreased in the si-SNHG11 group, and the tumor weight and volume were decreased, the expression of N-cadherin was decreased, and the apoptosis rate and the expression of E-cadherin protein were increased (P<0.05). Compared with the si-SNHG11+anti-NC group, the proliferation, migration and invasion ability of SKOV3 cells were increased in the si-SNHG11+anti-miR-184 group, the tumor weight and volume were increased, and the expression of N-cadherin protein was increased, and the apoptosis rate and E-cadherin protein expression were decreased (P<0.05). Compared with the miR-NC group, the proliferation, migration and invasion ability of SKOV3 cells were decreased in the miR-184 mimics group, the tumor weight and volume were decreased, the expression of N-cadherin protein was decreased, while the apoptosis rate and expression level of E-cadherin protein were increased (P<0.05). Compared with the miR-184 mimics+pcDNA group, the proliferation, migration and invasion ability of SKOV3 cells were increased in the miR-184mimics+CARM1 group. The tumor weight and volume were increased, and the expression of N-cadherin protein was increased, while the apoptosis rate and E-cadherin protein expression were decreased (P<0.05). LncRNA SNHG11 targetly regulated miR-184/CARM1 axis. Conclusion LncRNA SNHG11 promotes the growth of ovarian cancer by regulating miR-184/CARM1 signal axis.

Key words: ovarian neoplasms, neoplasm invasiveness, genetic therapy, long non-coding RNA small nucleolar RNA host gene 11, microRNA-184, coactivator-associated arginine methyltransferase 1

中图分类号:

R737.31

图/表 14

表1 不同卵巢癌细胞系中LncRNA SNHG11与miR-184表达水平比较（n=6，$\bar{x}±s$）

Tab.1 Comparison of expression levels of LncRNA SNHG11 and miR-184 between different ovarian cancer cell lines

细胞系	LncRNA SNHG11	miR-184
IOSE80	1.01±0.10	1.02±0.13
Hey	1.66±0.32^a	0.71±0.08^a
ES2	2.23±0.37^a	0.47±0.05^ab
SKOV3	3.25±0.54^abc	0.23±0.04^abc
A2780	1.93±0.41^ad	0.52±0.06^abd
F	28.717^＊＊	84.242^＊＊

图1 抑制LncRNA SNHG11表达对SKOV3细胞增殖的影响 F24 h=14.667，F48 h=37.141，F72 h=41.841，均P<0.01；a与si-NC组比较，b与si-SNHG11+anti-NC组比较，P<0.05。

Fig.1 Effect of inhibiting the expression of LncRNA SNHG11 on the proliferation of SKOV3 cells

图2 抑制LncRNA SNHG11表达后各组SKOV3细胞凋亡、迁移与侵袭比较 A：si-NC组；B：si-SNHG11组；C：si-SNHG11+anti-NC组；D：si-SNHG11+anti-miR-184组；图3同。

Fig.2 Comparison of apoptosis, migration and invasion of SKOV3 cells between the four groups after inhibiting lncRNA SNHG11 expression

图3 抑制LncRNA SNHG11表达后各组E-cadherin、N-cadherin蛋白表达比较

Fig.3 Comparison of E-cadherin and N-cadherin protein expression between the four groups after inhibiting LncRNA SNHG11 expression

表2 抑制LncRNA SNHG11表达后各组细胞增殖、凋亡、迁移及侵袭、瘤体质量与体积比较（n=6，$\bar{x}±s$）

Tab.2 Comparison of cell proliferation, apoptosis, migration and invasion, tumor mass and volume between the four groups after inhibition of LncRNA SNHG11 expression

组别	细胞凋亡率（%）	迁移细胞数（个/视野）	侵袭细胞数（个/视野）	E-cadherin	N-cadherin	瘤体质量（g）	瘤体体积（mm³）
si-NC组	2.43±0.78	145.27±8.31	126.53±7.23	0.21±0.04	1.13±0.12	1.53±0.32	1 258.62±35.46
si-SNHG11组	25.32±4.61^a	68.33±4.68^a	54.37±4.36^a	0.87±0.08^a	0.51±0.07^a	0.81±0.25^a	423.68±20.46^a
si-SNHG11+anti-NC组	23.65±3.82	65.27±4.75	57.70±5.21	0.83±0.09	0.47±0.08	0.87±0.27	411.32±18.42
si-SNHG11+anti-miR-184组	12.47±2.66^bc	123.63±8.47^bc	106.43±6.13^bc	0.37±0.05^bc	1.01±0.10^bc	1.33±0.28^bc	734.45±26.23^bc
F	62.853^＊＊	207.937^＊＊	227.120^＊＊	140.731^＊＊	77.176^＊＊	9.359^＊＊	1 398.970^＊＊

图4 LncRNA SNHG11与miR-184结合位点预测

Fig.4 Predicted binding sites of LncRNA SNHG11 and miR-184

表3 各组SKOV3 细胞LncRNA SNHG11、miR-184相对表达水平比较（n=6，$\bar{x}±s$）

Tab.3 Expression of LncRNA SNHG11 and miR-184 in SKOV3 cells in each group

组别	LncRNA SNHG11	miR-184
si-NC组	1.00±0.10	1.01±0.11
si-SNHG11组	0.41±0.06^a	1.67±0.23^a
si-SNHG11+anti-NC组	0.43±0.07	1.72±0.25
si-SNHG11+anti-miR-184组	0.45±0.06	1.05±0.12^bc
F	88.498^＊＊	25.047^＊＊

图5 过表达miR-184对SKOV3细胞增殖的影响 F24 h=16.476，F48 h=38.227，F72 h=46.751，均P<0.01；a与miR-NC组比较， b与miR-184 mimics+pcDNA组比较，P<0.05。

Fig.5 Effect of over-expression of miR-184 on proliferation of SKOV3 cells

图6 过表达miR-184后各组SKOV3细胞凋亡、迁移与侵袭比较 A：miR-NC组；B：miR-184 mimics组；C：miR-184 mimics+pcDNA组；D：miR-184 mimics+CARM1组。

Fig.6 Comparison of apoptosis, migration and invasion of SKOV3 cells between the four groups after over-expression of miR-184

图7 过表达miR-184后各组E-cadherin、N-cadherin蛋白表达比较 A：miR-NC组；B：miR-184 mimics组；C：miR-184 mimics+pcDNA组；D：miR-184 mimics+CARM1组；图9同。

Fig.7 Comparison of E-cadherin and N-cadherin protein expression between the four groups after over-expression of miR-184

表4 过表达miR-184后各组SKOV3细胞增殖、凋亡、迁移及侵袭、瘤体质量与体积比较（n=6，$\bar{x}±s$）

Tab.4 Comparison of proliferation, apoptosis, migration, invasion, tumor mass and volume of SKOV3 cells between the four groups after over-expressing miR-184

组别	细胞凋亡率（%）	迁移细胞数（个/视野）	侵袭细胞数（个/视野）	E-cadherin	N-cadherin	瘤体质量（g）	瘤体体积（mm³）
miR-NC组	1.95±0.41	137.40±8.23	123.73±7.51	0.23±0.05	1.15±0.13	1.57±0.34	1 271.62±40.21
miR-184 mimics组	24.72±4.65^a	72.37±6.14^a	56.40±5.81^a	0.81±0.07^a	0.47±0.06^a	0.83±0.25^a	435.68±23.21^a
miR-184 mimics+pcDNA组	22.47±4.83	69.57±5.93	54.37±5.08	0.84±0.08	0.45±0.05	0.85±0.28	428.45±20.35
miR-184 mimics+CARM1组	11.26±2.33^bc	114.37±6.55^bc	103.23±6.35^bc	0.32±0.04^bc	1.05±0.12^bc	1.31±0.34^bc	718.45±24.21^bc
F	52.944^＊＊	143.205^＊＊	183.624^＊＊	159.481^＊＊	88.727^＊＊	8.471^＊＊	1 191.357^＊＊

图8 miR-184与CARM1的靶向关系验证

Fig.8 Verification of the targeting relationship between miR-184 and CARM1

表5 过表达miR-184后各组miR-184、CARM1 mRNA及蛋白表达比较（n=6，$\bar{x}±s$）

Tab.5 Comparison of miR-184, CARM1 mRNA and protein expression between the four groups after over-expression of miR-184

组别	miR-184	CARM1 mRNA	CARM1蛋白
miR-NC组	1.01±0.12	1.03±0.10	1.13±0.12
miR-184 mimics组	2.47±0.52^a	0.41±0.05^a	0.27±0.03^a
miR-184 mimics+pcDNA组	2.46±0.47	0.38±0.04	0.25±0.04
miR-184 mimics+CARM1组	2.45±0.51	0.98±0.09^bc	1.03±0.11^bc
F	16.475^＊＊	134.703^＊＊	186.924^＊＊

图9 过表达miR-184后各组SKOV3细胞CARM1蛋白表达比较

Fig.9 Comparison of CARM1 protein expression in SKOV3 cells between the four groups after over-expression of miR-184

参考文献 17

[1]	WU Y, GU W, HAN X, et al. LncRNA PVT1 promotes the progression of ovarian cancer by activating TGF-β pathway via miR-148a-3p/AGO1 axis[J]. J Cell Mol Med, 2021, 25(17):8229-8243. doi:10.1111/jcmm.16700.
[2]	LIU G, CHEN L, REN H, et al. Seven genes based novel signature predicts clinical outcome and platinum sensitivity of high grade Ⅲc serous ovarian carcinoma[J]. Int J Biol Sci, 2018, 14(14):2012-2022. doi:10.7150/ijbs.28249.
[3]	BRAGA E A, FRIDMAN M V, MOSCOVTSEV A A, et al. LncRNAs in ovarian cancer progression,metastasis,and main pathways:ceRNA and alternative mechanisms[J]. Int J Mol Sci, 2020, 21(22):8855-8899. doi:10.3390/ijms21228855.
[4]	XIE Q, ZHAO S, KANG R, et al. LncRNA SNHG11 facilitates prostate cancer progression through the upregulation of IGF 1R expression and by sponging miR 184[J]. Int J Mol Med, 2021, 48(3):182-193. doi:10.3892/ijmm.2021.5015.
[5]	QIN C Z, LOU X Y, LV Q L, et al. MicroRNA-184 acts as a potential diagnostic and prognostic marker in epithelial ovarian cancer and regulates cell proliferation,apoptosis and inflammation[J]. Pharmazie, 2015, 70(10):668-673.
[6]	KARAKASHEV S, ZHANG R. Targeting CARM1 in ovarian cancer with EZH2 and PARP inhibitors[J]. Mol Cell Oncol, 2020, 7(4):1760675. doi:10.1080/23723556.2020.1760675.
[7]	吴超, 王彩星, 韩瑜娇, 等. LncRNA SNHG15靶向miR-153对乳腺癌细胞线粒体途径凋亡的影响[J]. 中国肿瘤生物治疗杂志, 2020, 27(10):1087-1092.
	WU C, WANG C X, HAN Y J, et al. Effect of lncRNA SNHG15 targeting miR-153 on mitochondrial apoptosis in breast cancer cells[J]. Chin J Cancer Biother, 2020, 27(10):1087-1092. doi:10.3872/j.issn.1007-385x.2020.10.003.
[8]	YU L, ZHANG W, WANG P, et al. LncRNA SNHG11 aggravates cell proliferation and migration in triple-negative breast cancer via sponging miR-2355-5p and targeting CBX5[J]. Exp Ther Med, 2021, 22(2):892. doi:10.3892/etm.2021.10324.
[9]	GENG Y B, XU C, WANG Y, et al. Long non-coding RNA SNHG11 promotes cell proliferation,invasion and migration in glioma by targeting miR-154-5p[J]. Eur Rev Med Pharmacol Sci, 2020, 24(9):4901-4908. doi:10.26355/eurrev_202005_21179.
[10]	XU L, HUAN L, GUO T, et al. LncRNA SNHG11 facilitates tumor metastasis by interacting with and stabilizing HIF-1α[J]. Oncogene, 2020, 39(46):7005-7018. doi:10.1038/s41388-020-01512-8.
[11]	FAN L, LEI H, ZHANG S, et al. Non-canonical signaling pathway of SNAI2 induces EMT in ovarian cancer cells by suppressing miR-222-3p transcription and upregulating PDCD10[J]. Theranostics, 2020, 10(13):5895-5913. doi:10.7150/thno.43198.
[12]	CHENG R, LU X, XU C, et al. SNHG11 contributes to NSCLC cell growth and migration by targeting miR-485-5p/BSG axis[J]. Biomed Pharmacother, 2020, 128:110324. doi:10.1016/j.biopha.2020.

[13]	HUANG W, HUANG F, LEI Z, et al. LncRNA SNHG11 promotes proliferation,migration,apoptosis,and autophagy by regulating hsa-miR-184/AGO2 in HCC[J]. Onco Targets Ther, 2020, 13(1):413-421. doi:10.2147/OTT.S237161.
[14]	TAN G G, XU C, ZHONG W K, et al. MiR-184 delays cell proliferation,migration and invasion in prostate cancer by directly suppressing DLX1[J]. Exp Ther Med, 2021, 22(4):1163. doi:10.3892/etm.2021.10597.
[15]	ZHU H M, JIANG X S, LI H Z, et al. MiR-184 inhibits tumor invasion,migration and metastasis in nasopharyngeal carcinoma by targeting Notch2[J]. Cell Physiol Biochem, 2018, 49(4):1564-1576. doi:10.1159/000493459.
[16]	LIN J, LIU H, FUKUMOTO T, et al. Targeting the IRE1α/XBP1s pathway suppresses CARM1-expressing ovarian cancer[J]. Nat Commun, 2021, 12(1):5321-5335. doi:10.1038/s41467-021-25684-3.
[17]	ZHENG M, NIU Y, BU J, et al. ESRP1 regulates alternative splicing of CARM1 to sensitize small cell lung cancer cells to chemotherapy by inhibiting TGF-β/Smad signaling[J]. Aging (Albany NY), 2021, 13(3):3554-3572. doi:10.18632/aging.202295.

LncRNA SNHG11通过抑制miR-184/CARM1信号轴促进卵巢癌生长

Influences of lncRNA SNHG11 on proliferation, apoptosis, migration and invasion of ovarian cancer cells by regulating miR-184/CARM1 signaling axis

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 14

参考文献 17

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张晋玮, 王燕, 王通. miR-107对口腔鳞癌细胞系CAL27增殖、侵袭及迁移的影响[J]. 天津医药, 2024, 52(9): 897-899.
[2]	汪爱华, 张飞忠, 王红英. 麝香酮调节SHH介导的自噬对卵巢癌细胞恶性进展的影响[J]. 天津医药, 2024, 52(2): 142-147.
[3]	喻萍, 周敏, 苏丹. 卵巢癌化疗耐药预测模型的建立及效果评价[J]. 天津医药, 2024, 52(11): 1177-1182.
[4]	龙颖, 黄芳依, 韦有生. NGF/TrkA轴对宫颈癌SiHa细胞增殖、凋亡和侵袭的影响[J]. 天津医药, 2023, 51(8): 809-813.
[5]	王玉宁, 宋聚星, 田志刚, 郝国荣, 申浩. 白皮杉醇调控miR-106b-5p/RUNX3轴对宫颈癌细胞迁移及侵袭的影响[J]. 天津医药, 2023, 51(8): 814-819.
[6]	宁寅宽, 刘林志, 陈贤平. BMP2重组慢病毒转染兔BMSCs后细胞矿化的实验研究[J]. 天津医药, 2023, 51(5): 454-459.
[7]	李娟, 倪惠华. GPR120和GPR40表达与卵巢癌临床病理特征及预后的关系[J]. 天津医药, 2023, 51(5): 522-526.
[8]	刘宏伟, 朱奕, 向玲宝, 熊洪, 陈瑞琦. miR-338-5p通过靶向TSHZ3促进膀胱癌细胞增殖、迁移和侵袭[J]. 天津医药, 2023, 51(10): 1025-1031.
[9]	张丛, 冯华, 黄小龙, 王旋. 蔓荆子黄素调控miR-378/PRRX1轴对胃癌生物学行为的影响[J]. 天津医药, 2023, 51(10): 1040-1047.
[10]	邢佳侬, 梁卓, 邢爱君, 刘俊兰, 彭宏超, 张天桦, 张春来. LncRNA MIAT靶向调节miR-128-3p对心房颤动大鼠心室重构和心肌纤维化的影响[J]. 天津医药, 2022, 50(9): 932-937.
[11]	陈霄, 吴小颖, 安明. lncRNA SOX21-AS1的表达对卵巢癌细胞增殖和转移能力的影响及机制研究[J]. 天津医药, 2022, 50(12): 1254-1258.
[12]	李力, 郭祥翠, 王倩青, 李君, 郜智慧. 红芪多糖对卵巢癌SKOV3细胞凋亡、生长和运动能力的影响#br# #br#[J]. 天津医药, 2021, 49(5): 455-459.
[13]	鞠薇薇, 于生金, 林黎娟, 邵志翔, 张奇芳, 江黎黎. 尼克酰胺-N-甲基转移酶在肺腺癌间质中的表达及其生物学功能 #br#[J]. 天津医药, 2021, 49(2): 113-118.
[14]	刘晋芳, 徐小燕, 周儒奎, 徐慧超, 高艳, 苗宇船△. 下调TMEM97对卵巢癌细胞SKOV3增殖、凋亡的影响及其相关机制探讨[J]. 天津医药, 2020, 48(8): 695-699.
[15]	陈国庆, 叶萍, 徐玲, 谢晓英△. BNIP3介导的线粒体自噬对低氧环境下卵巢癌HO-8910PM细胞侵袭转移的影响#br#[J]. 天津医药, 2020, 48(8): 700-704.