Effects of lncRNA SOX21-AS1 expression on proliferation and metastasis of ovarian cancer cells and its mechanism

doi:10.11958/20220316

Abstract

Abstract:

Objective To study the effect of long non-coding RNA SRY-box transcription factor 21 antisense RNA 1 (lncRNA SOX21-AS1) on the proliferation and metastasis of ovarian cancer cells and its mechanism. Methods A total of 75 samples of ovarian cancer and 75 samples of adjacent paracancerous tissues were selected. Ovarian cancer cell lines SKOV3, A2780, OVCR3 and human normal ovarian epithelial cells HOSE were selected as the experimental objects. The expression levels of lncRNA SOX21-AS1 in tissues and cells were detected by qPCR. The cells were divided into the si-NC group and the si-SOX21-AS1 group according to whether they interfered with the expression of lncRNA SOX21-AS1. MTS assay and plate cloning assay were used to detect cell proliferation ability, and Transwell assay was used to detect cell transfer ability. TOP/FOP luciferase assay and Western blot assay were used to detect Wnt/β-catenin signaling pathway activity and related protein expression levels in cells. Results Compared with adjacent tissues, the expression of lncRNA SOX21-AS1 was significantly up-regulated in ovarian cancer tissues (P<0.05). Compared with normal ovarian epithelial cells HOSE, the expression of lncRNA SOX21-AS1 was significantly up-regulated in ovarian cancer cells (P<0.05). Compared with patients with FIGO stage I-II and patients with no lymph node metastasis, the relative expression level of lncRNA SOX21-AS1 was significantly higher in patients with FIGO stage III-IV and patients with lymph node metastasis (P<0.05). Interfering with the expression of lncRNA SOX21-AS1 significantly inhibited cell proliferation and metastasis, Wnt/β-catenin signaling pathway activity and Wnt/β-catenin signaling pathway related protein expression (P<0.05). Conclusion lncRNA SOX21-AS1 is highly expressed in ovarian cancer tissues and cells. Interfering with the expression of lncRNA SOX21-AS1 significantly inhibits the proliferation and metastasis of ovarian cancer cells.

Key words: ovarian neoplasms, cell proliferation, neoplasm metastasis, gene expression regulation, neoplastic, lncRNA SOX21-AS1

CLC Number:

R737.31

Figures/Tables 5

References 20

[1]	SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics,2019[J]. CA Cancer J Clin, 2019, 69(1):7-34. doi:10.3322/caac.21551.
[2]	GUPTA K K, GUPTA V K, NAUMANN R W. Ovarian cancer:screening and future directions[J]. Int J Gynecol Cancer, 2019, 29(1):195-200. doi:10.1136/ijgc-2018-000016.
[3]	杨维娜, 徐燕颖. 长链非编码RNA在卵巢癌中的研究进展[J]. 山东医药, 2020, 60(29):91-93.
	YANG W N, XU Y Y. Research progress of long chain noncoding RNA in ovarian cancer[J]. Shandong Med J, 2020, 60(29):91-93. doi:10.3969/j.issn.1002-266X.2020.29.027.
[4]	MACDONALD W A, MANN M R W. Long noncoding RNA functionality in imprinted domain regulation[J]. PLoS Genet, 2020, 16(8):e1008930. doi:10.1371/journal.pgen.1008930.
[5]	ZHANG X, ZHAO X, LI Y, et al. Long noncoding RNA SOX21-AS1 promotes cervical cancer progression by competitively sponging miR-7/VDAC1[J]. J Cell Physiol, 2019, 234(10):17494-17504. doi:10.1002/jcp.28371.
[6]	SHENG X Y, WANG C H, WANG C F, et al. Long-chain non-coding SOX21-AS1 promotes proliferation and migration of breast cancer cells through the PI3K/AKT signaling pathway[J]. Cancer Manag Res, 2020, 12(11):11005-11014. doi:10.2147/CMAR.S270464.
[7]	武金玉, 张苑珑, 黄明莉, 等. Wnt/β-catenin通路在卵巢癌中的调控机制研究进展[J]. 现代妇产科进展, 2018, 27(4):311-313,317.
	WU J Y, ZHANG Y L, HUANG M L, et al. Research progress on the regulatory mechanism of Wnt/β-catenin pathway in ovarian cancer[J]. Prog Obstet Gyne, 2018, 27(4):311-313,317. doi:10.13283/j.cnki.xdfckjz.2018.04.016.
[8]	GAI S Y, YUAN Z H. Long non-coding RNA SOX21-AS1 promotes cell proliferation and invasion through upregulating PAK7 expression by sponging miR-144-3p in glioma cells[J]. Neoplasma, 2020, 67(2):333-343. doi:10.4149/neo_2020_190509N412.
[9]	WANG J Y, LU A Q, CHEN L J. LncRNAs in ovarian cancer[J]. Clin Chim Acta, 2019, 90(5):17-27. doi:10.1016/j.cca.2018.12.013.
[10]	MORAND S, DEVANABOYINA M, STAATS H, et al. Ovarian cancer immunotherapy and personalized medicine[J]. Int J Mol Sci, 2021, 22(12):6532. doi:10.3390/ijms22126532.
[11]	LIM S M, SYN N L, CHO B C, et al. Acquired resistance to EGFR targeted therapy in non-small cell lung cancer:Mechanisms and therapeutic strategies[J]. Cancer Treat Rev, 2018, 65(8):1-10. doi:10.1016/j.ctrv.2018.02.006.
[12]	SAKACH E, O'REGAN R, MEISEL J, et al. Molecular classification of triple negative breast cancer and the emergence of targeted therapies[J]. Clin Breast Cancer, 2021, 21(6):509-520. doi:10.1016/j.clbc.2021.09.003.
[13]	BARTOLETTI M, PELIZZARI G, GERRATANA L, et al. Bevacizumab or PARP-inhibitors maintenance therapy for platinum-sensitive recurrent ovarian cancer:a network Meta-analysis[J]. Int J Mol Sci, 2020, 21(11):3805. doi:10.3390/ijms21113805.
[14]	LIU X, SONG J, KANG Y, et al. Long noncoding RNA SOX21-AS1 regulates the progression of triple-negative breast cancer through regulation of miR-520a-5p/ORMDL3 axis[J]. J Cell Biochem, 2020, 121(11):4601-4611. doi:10.1002/jcb.29674.
[15]	ZHANG L, FANG Y, CHENG X, et al. Silencing of long noncoding RNA SOX21-AS1 relieves neuronal oxidative stress injury in mice with alzheimer's disease by upregulating FZD3/5 via the Wnt signaling pathway[J]. Mol Neurobiol, 2019, 56(5):3522-3537. doi:10.1007/s12035-018-1299-y.
[16]	WEI C, WANG H, XU F, et al. LncRNA SOX21-AS1 is associated with progression of hepatocellular carcinoma and predicts prognosis through epigenetically silencing p21[J]. Biomed Pharmacother, 2018, 104(8):137-144. doi:10.1016/j.biopha.2018.05.010.
[17]	ZHANG J, HOU T, QI X, et al. SOX21-AS1 is associated with clinical stage and regulates cell proliferation in nephroblastoma[J]. Biosci Rep, 2019, 39(5):BSR20190602. doi:10.1042/BSR20190602.
[18]	CHEN H, CHEN J. LncRNA SOX21-AS1 promotes the growth and invasiveness of osteosarcoma cells through miR-7-5p/IRS2 regulatory network[J]. Arch Med Res, 2021, 52(3):294-303. doi:10.1016/j.arcmed.2020.11.007.
[19]	LI L, MENG D, WANG R. Long non-coding RNA SOX21-AS1 enhances the stemness of breast cancer cells via the Hippo pathway[J]. FEBS Open Bio, 2021, 11(1):251-264. doi:10.1002/2211-5463.13015.
[20]	LECARPENTIER Y, SCHUSSLER O, HÉBERT J L, et al. Multiple targets of the canonical WNT/β-Catenin signaling in cancers[J]. Front Oncol, 2019, 9(11):1248. doi:10.3389/fonc.2019.01248.

临床特征	n	lncRNA SOX21-AS1相对表达量	t
年龄（岁）
≤60	45	1.65±0.31	0.658
>60	30	1.70±0.34	0.658
组织分级
G1-2	34	1.61±0.29	1.436
G3	41	1.72±0.36	1.436
FIGO分期
Ⅰ-Ⅱ	35	1.45±0.24	5.193^＊＊
Ⅲ-Ⅳ	40	1.83±0.37	5.193^＊＊
淋巴结转移
有	44	1.79±0.34	3.905^＊＊
无	31	1.50±0.28	3.905^＊＊
远处转移
有	28	1.75±0.34	1.829
无	47	1.62±0.27	1.829

临床特征	n	lncRNA SOX21-AS1相对表达量	t
年龄（岁）
≤60	45	1.65±0.31	0.658
>60	30	1.70±0.34	0.658
组织分级
G1-2	34	1.61±0.29	1.436
G3	41	1.72±0.36	1.436
FIGO分期
Ⅰ-Ⅱ	35	1.45±0.24	5.193^＊＊
Ⅲ-Ⅳ	40	1.83±0.37	5.193^＊＊
淋巴结转移
有	44	1.79±0.34	3.905^＊＊
无	31	1.50±0.28	3.905^＊＊
远处转移
有	28	1.75±0.34	1.829
无	47	1.62±0.27	1.829

组别	lncRNA SOX21-AS1相对表达量	SKOV3增殖能力（A₄₉₀）			克隆团形成数（个/视野）	细胞转移数目（个/视野）	TOP/FOP荧光素酶活性
组别	lncRNA SOX21-AS1相对表达量	24 h	48 h	72 h	克隆团形成数（个/视野）	细胞转移数目（个/视野）	TOP/FOP荧光素酶活性
si-NC组	0.98±0.02	0.55±0.05	0.81±0.05	1.30±0.07	70.67±6.81	92.33±12.54	0.97±0.03
si-SOX21-AS1组	0.38±0.07	0.47±0.04	0.52±0.03	0.73±0.04	51.33±4.32	50.67±8.56	0.54±0.08
t	14.275^＊＊	2.164	8.614^＊＊	12.246^＊＊	4.154^＊	4.752^＊	8.717^＊＊

组别	lncRNA SOX21-AS1相对表达量	SKOV3增殖能力（A₄₉₀）			克隆团形成数（个/视野）	细胞转移数目（个/视野）	TOP/FOP荧光素酶活性
组别	lncRNA SOX21-AS1相对表达量	24 h	48 h	72 h	克隆团形成数（个/视野）	细胞转移数目（个/视野）	TOP/FOP荧光素酶活性
si-NC组	0.98±0.02	0.55±0.05	0.81±0.05	1.30±0.07	70.67±6.81	92.33±12.54	0.97±0.03
si-SOX21-AS1组	0.38±0.07	0.47±0.04	0.52±0.03	0.73±0.04	51.33±4.32	50.67±8.56	0.54±0.08
t	14.275^＊＊	2.164	8.614^＊＊	12.246^＊＊	4.154^＊	4.752^＊	8.717^＊＊

组别	Wnt3a	β-catenin	CyclinD1	cMyc	MMP-7
si-NC组	0.91±0.06	0.47±0.03	0.52±0.06	1.18±0.14	0.98±0.10
si-SOX21-AS1组	0.36±0.05	0.31±0.02	0.11±0.03	0.19±0.02	0.27±0.02
t	12.197^＊＊	7.686^＊	10.586^＊＊	12.125^＊＊	12.059^＊＊