Effects of kaempferol regulating VPS9D1-AS1/miR-377-3p on proliferation and apoptosis of cervical cancer cell line SiHa

doi:10.16352/j.issn.1001-6325.2023.07.1069

Abstract

Abstract: Objective To investigate the effect of kaempferol on regulation of long non-coding RNA(lncRNA) vps9d1 antisense RNA 1 (VPS9D1-AS1) /miR-377-3p and on biological behavior of cervical cancer cells. Methods The cervical cancer cell line SiHa was divided into control group, low, medium and high dose of kaempferol group (5 μmol/L、10 μmol/L and 20 μmol/L kaempferol), si-NC group (transfected si-NC), si-VPS9D1-AS1 group (transfected si-VPS9D1-AS1), kaempferol + pcDNA-VPS9D1-AS1 group (20 mg/L kaempferol+transfected pcDNA-VPS9D1-AS1), kaempferol + anti-miR-377-3p group (20 mg/L kaempferol + transfected anti-miR-377-3p).VPS9D1-AS1, miR-377-3p expression, cell activity and colony formation were measured by RT-qPCR, MTT assay and colony formation assay; Cell apoptosis, migration, invasion and Bax/Bcl-2 expression were measured by flow cytometry, scratch test, Transwell test and Western blot. Luciferase activity assay was used to evaluate the targeting effect of VPS9D1-AS1 on miR-377-3p. Results Compared with the control, low, medium and high doses of kaempferol decreased the expression level of VPS9D1-AS1, the number of colony formation, cell activity, Bcl-2 protein expression level, migration distance and the number of invasive cells in SiHa cells, and increased the expression level of miR-377-3p, apoptosis rate as well as Bax protein expression level in a concentration dependent manner (P<0.05). After VPS9D1-AS1 was silenced in SiHa cells, the expression level of miR-377-3p, apoptosis rate and Bax protein expression level were higher than those in si-NC group; The colony forming number, Bcl-2 protein expression, cell activity, migration distance and the accounting of invasive cells in si-NC group were significantly(P<0.05) lower than those in si-NC group. VPS9D1-AS1 targeted at miR-377-3p. The effects of kaempferol treated SiHa on proliferation, apoptosis, migration and invasion were reversed by over-expression of VPS9D1-AS1 or inhibition of miR-377-3p. Conclusions Kaempferol can inhibit the proliferation, migration and invasion of cervical cancer cells and accelerate apoptosis by down regulating VPS9D1-AS1 targeted at miR-377-3p.

Key words: cervical cancer, kaempferol, cell biological behavior, VPS9D1-AS1, miR-377-3p

CLC Number:

R73-36

ZHANG Yuxin, ZHU Ziwei, ZHANG Yan, HU Yuhong. Effects of kaempferol regulating VPS9D1-AS1/miR-377-3p on proliferation and apoptosis of cervical cancer cell line SiHa[J]. Basic & Clinical Medicine, 2023, 43(7): 1069-1078.

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URL: http://journal11.magtechjournal.com/Jwk_jcyxylc/EN/10.16352/j.issn.1001-6325.2023.07.1069

http://journal11.magtechjournal.com/Jwk_jcyxylc/EN/Y2023/V43/I7/1069

References

[1] Koh WJ, Abu-Rustum NR, Bean S, et al. Cervical cancer, version 3.2019, NCCN clinical practice guide-lines in oncology[J]. J Natl Compr Canc Netw, 2019, 17:64-84.
[2] Siegel RL, Miller KD, Jemal A.Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69:7-34.
[3] Imran M, Salehi B, Sharifi-Rad J, et al. Kaempferol: a key emphasis to its anticancer potential[J]. Molecules, 2019, 24:2277-2292.
[4] Ren J, Lu Y, Qian Y, et al. Recent progress regarding kaempferol for the treatment of various diseases[J]. Exp Ther Med, 2019, 18:2759-2776.
[5] 于丽秀, 邓亚卉, 邓斌,等. 山萘酚对卵巢癌细胞增殖、凋亡的影响及机制研究[J]. 中国医院药学杂志, 2019, 39:2040-2043.
[6] 李鹰飞, 曾世彬, 邱华平, 等. 山奈酚对乳腺癌细胞增殖及诱导凋亡的作用研究及机制[J]. 中国临床药理学杂志, 2020, 36:113-116.
[7] 张敬, 史晓宇, 孟玮,等. 山萘酚通过下调ERRα抑制非小细胞肺癌A549细胞的侵袭和迁移[J]. 中国肿瘤生物治疗杂志, 2018, 25:1230-1236.
[8] Ala U.Competing endogenous RNAs, non-coding RNAs and diseases: an intertwined story[J]. Cells, 2020, 9:1574-1596.
[9] Liu H, Zhang X, Jin X, et al. Long noncoding RNA VPS9D1-AS1 sequesters microRNA-525-5p to promote the oncogenicity of colorectal cancer cells by upregulating HMGA1[J]. Cancer Manag Res, 2020, 12:9915-9928.
[10] Lin L, Que Y, Lu P, et al. Chidamide inhibits acute myeloid leukemia cell proliferation by lncRNA VPS9D1-AS1 downregulation via MEK/ERK signaling pathway[J]. Front Pharmacol, 2020, 11:589-601.
[11] Meng QH, Li Y, Kong C, et al. Circ_0000388 exerts oncogenic function in cervical cancer cells by regulating miR-337-3p/TCF12 Axis[J]. Cancer Biother Radiopharm, 2021, 36:58-69.
[12] Zhang XY, Dong XM, Wang FP. miR-377-3p inhibits cell metastasis and epithelial-mesenchymal transition in cervical carcinoma through targeting SGK3[J]. Eur Rev Med Pharmacol Sci, 2020, 24:4687-4696.
[13] 谢玉海,朵海珍,王学军. 利多卡因通过lncRNA H19/miR-671-5p分子轴调控胃癌细胞增殖、迁移及侵袭[J]. 中国免疫学杂志,2022,38:1475-1479.
[14] Han X, Liu CF, Gao N, et al. RETRACTED: Kaemp-ferol suppresses proliferation but increases apoptosis and autophagy by up-regulating microRNA-340 in human lung cancer cells[J]. Biomed Pharmacother, 2018,108:809-816.
[15] Xu Y, Jiang T, Wang C, et al. Sinomenine hydrochloride exerts antitumor outcome in ovarian cancer cells by inhibition of long non-coding RNA HOST2 expression[J]. Artif Cells Nanomed Biotechnol, 2019, 47:4131-4138.