Berberine inhibits the proliferation, invasion and migration of endometrial stromal cells by downregulating miR‑429

Gu,Yongjuan; Zhou,Zhigang

doi:10.3892/mmr.2021.12055

Berberine inhibits the proliferation, invasion and migration of endometrial stromal cells by downregulating miR‑429

Authors:
- Yongjuan Gu
- Zhigang Zhou
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Jianhu Hospital Affiliated to Nantong University, Yancheng, Jiangsu 224700, P.R. China, Institution of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China
Published online on: March 31, 2021 https://doi.org/10.3892/mmr.2021.12055
Article Number: 416
Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Endometriosis (EM) is a common gynecological disease, and its pathological process is accompanied by the migration and proliferation of uterine cells. Berberine (BBR) has been shown to exhibit antitumor activity; however, the effects of BBR on EM have seldom been reported to date. The expression of microRNA (miR)‑429 is upregulated in EM and miR‑429 can be used as a target for drug regulation of cancer cells. Whether BBR plays a regulatory role in EM by targeting miR‑429 has not been reported. Thus, the aim of the present study was to determine the effects of BBR on EM cells. The survival rate of immortalized human endometrial stromal cells (HESCs) was determined using a Cell Counting Kit‑8 assay. A colony formation assay was used to detect the rate of cell proliferation. The expression levels of proliferation‑related proteins, including proliferation marker protein Ki‑67 (Ki‑67) and proliferating cell nuclear antigen (PCNA), were detected by reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. Wound healing and Transwell assays were performed to detect cell migration and invasion, and western blotting was used to detect the expression of the migration‑ and invasion‑related proteins, including matrix metalloproteinase (MMP)2, MMP4 and MMP9. The expression of miR‑429 was detected by RT‑qPCR following its overexpression via cell transfection. The results revealed that treatment with 80 µM BBR significantly inhibited cell proliferation and colony formation, and inhibited the expression of Ki‑67 and PCNA proteins in HESCs. BBR inhibited cell invasion and migration, as well as the expression of MMP2, MMP4 and MMP9. In this process, it was found that the expression of miR‑429 decreased following treatment of the cells with BBR, whereas the inhibitory effects of BBR on cell proliferation, invasion and migration were suppressed following the overexpression of miR‑429. Overall, the findings of the present study indicated that BBR inhibited the proliferation, invasion and migration of HESCs by downregulating the expression of miR‑429.

View Figures

View References

1	Gordts S, Koninckx P and Brosens I: Pathogenesis of deep endometriosis. Fertil Steril. 108:872–885. 2017. View Article : Google Scholar : PubMed/NCBI
2	Czyzyk A, Podfigurna A, Szeliga A and Meczekalski B: Update on endometriosis pathogenesis. Minerva Ginecol. 69:447–461. 2017.PubMed/NCBI
3	Li J, Ma J, Fei X, Zhang T, Zhou J and Lin J: Roles of cell migration and invasion mediated by twist in endometriosis. J Obstet Gynaecol Res. 45:1488–1496. 2019. View Article : Google Scholar : PubMed/NCBI
4	Kodaman PH: Current strategies for endometriosis management. Obstet Gynecol Clin North Am. 42:87–101. 2015. View Article : Google Scholar : PubMed/NCBI
5	Grimstad FW and Carey E: Periclitoral endometriosis: The dilemma of a chronic disease invading a rare location. J Minim Invasive Gynecol. 22:684–686. 2015. View Article : Google Scholar : PubMed/NCBI
6	Jin Y, Khadka DB and Cho WJ: Pharmacological effects of berberine and its derivatives: A patent update. Expert Opin Ther Pat. 26:229–243. 2016. View Article : Google Scholar : PubMed/NCBI
7	Liu L, Fan J, Ai G, Liu J, Luo N, Li C and Cheng Z: Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells. Biol Res. 52:372019. View Article : Google Scholar : PubMed/NCBI
8	Du J, Sun Y, Lu YY, Lau E, Zhao M, Zhou QM and Su SB: Berberine and evodiamine act synergistically against human breast cancer MCF-7 cells by inducing cell cycle arrest and apoptosis. Anticancer Res. 37:6141–6151. 2017.PubMed/NCBI
9	Abrams SL, Follo MY, Steelman LS, Lertpiriyapong K, Cocco L, Ratti S, Martelli AM, Candido S, Libra M, Murata RM, et al: Abilities of berberine and chemically modified berberines to inhibit proliferation of pancreatic cancer cells. Adv Biol Regul. 71:172–182. 2019. View Article : Google Scholar : PubMed/NCBI
10	Wang Y and Zhang S: Berberine suppresses growth and metastasis of endometrial cancer cells via miR-101/COX-2. Biomed Pharmacother. 103:1287–1293. 2018. View Article : Google Scholar : PubMed/NCBI
11	Jin P, Zhang C and Li N: Berberine exhibits antitumor effects in human ovarian cancer cells. Anticancer Agents Med Chem. 15:511–516. 2015. View Article : Google Scholar : PubMed/NCBI
12	Wu G, Zheng H, Xu J, Guo Y, Zheng G, Ma C, Hao S, Liu X, Chen H, Wei S, et al: miR-429 suppresses cell growth and induces apoptosis of human thyroid cancer cell by targeting ZEB1. Artif Cells Nanomed Biotechnol. 47:548–554. 2019. View Article : Google Scholar : PubMed/NCBI
13	Dai W, He J, Zheng L, Bi M, Hu F, Chen M, Niu H, Yang J, Luo Y, Tang W and Sheng M: miR-148b-3p, miR-190b, and miR-429 regulate cell progression and act as potential biomarkers for breast cancer. J Breast Cancer. 22:219–236. 2019. View Article : Google Scholar : PubMed/NCBI
14	Han Y, Zhao Q, Zhou J and Shi R: miR-429 mediates tumor growth and metastasis in colorectal cancer. Am J Cancer Res. 7:218–233. 2017.PubMed/NCBI
15	Liu H, Huang C, Wu L and Wen B: Effect of evodiamine and berberine on miR-429 as an oncogene in human colorectal cancer. Onco Targets Ther. 9:4121–4127. 2016. View Article : Google Scholar : PubMed/NCBI
16	Braicu OL, Budisan L, Buiga R, Jurj A, Achimas-Cadariu P, Pop LA, Braicu C, Irimie A and Berindan-Neagoe I: miRNA expression profiling in formalin-fixed paraffin-embedded endometriosis and ovarian cancer samples. Onco Targets Ther. 10:4225–4238. 2017. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Meng X, Liu J, Wang H, Chen P and Wang D: MicroRNA-126-5p downregulates BCAR3 expression to promote cell migration and invasion in endometriosis. Mol Cell Endocrinol. 494:1104862019. View Article : Google Scholar : PubMed/NCBI
19	Garcia-Solares J, Dolmans MM, Squifflet JL, Donnez J and Donnez O: Invasion of human deep nodular endometriotic lesions is associated with collective cell migration and nerve development. Fertil Steril. 110:1318–1327. 2018. View Article : Google Scholar : PubMed/NCBI
20	Shimada H, Satohisa S, Kohno T, Takahashi S, Hatakeyama T, Konno T, Tsujiwaki M, Saito T and Kojima T: The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells. Oncotarget. 7:27735–27752. 2016. View Article : Google Scholar : PubMed/NCBI
21	Kim JJ, Kurita T and Bulun SE: Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev. 34:130–162. 2013. View Article : Google Scholar : PubMed/NCBI
22	Chen JJ, Xiao ZJ, Meng X, Wang Y, Yu MK, Huang WQ, Sun X, Chen H, Duan YG, Jiang X, et al: MRP4 sustains Wnt/β-catenin signaling for pregnancy, endometriosis and endometrial cancer. Theranostics. 9:5049–5064. 2019. View Article : Google Scholar : PubMed/NCBI
23	Kajiyama H, Suzuki S, Yoshihara M, Tamauchi S, Yoshikawa N, Niimi K, Shibata K and Kikkawa F: Endometriosis and cancer. Free Radic Biol Med. 133:186–192. 2019. View Article : Google Scholar : PubMed/NCBI
24	McCubrey JA, Lertpiriyapong K, Steelman LS, Abrams SL, Yang LV, Murata RM, Rosalen PL, Scalisi A, Neri LM, Cocco L, et al: Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY). 9:1477–1536. 2017. View Article : Google Scholar : PubMed/NCBI
25	Dai W, Mu L, Cui Y, Li Y, Chen P, Xie H and Wang X: Berberine promotes apoptosis of colorectal cancer via regulation of the long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2)/AU-binding factor 1 (AUF1)/B-cell CLL/lymphoma 2 (Bcl-2) axis. Med Sci Monit. 25:730–738. 2019. View Article : Google Scholar : PubMed/NCBI
26	Lo SN, Wang CW, Chen YS, Huang CC, Wu TS, Li LA, Lee IJ and Ueng YF: Berberine activates aryl hydrocarbon receptor but suppresses CYP1A1 induction through miR-21-3p stimulation in MCF-7 breast cancer cells. Molecules. 22:18472017. View Article : Google Scholar
27	Gao H, Sun X, Wang H and Zheng Y: Long noncoding RNA SNHG22 increases ZEB1 expression via competitive binding with microRNA-429 to promote the malignant development of papillary thyroid cancer. Cell Cycle. 19:1186–1199. 2020. View Article : Google Scholar : PubMed/NCBI
28	Cava C, Novello C, Martelli C, Lodico A, Ottobrini L, Piccotti F, Truffi M, Corsi F, Bertoli G and Castiglioni I: Theranostic application of miR-429 in HER2+ breast cancer. Theranostics. 10:50–61. 2020. View Article : Google Scholar : PubMed/NCBI