Curcumin inhibits prostate cancer progression by regulating the miR‑30a‑5p/PCLAF axis

Pan,Liang; Sha,Jian; Lin,Wenyao; Wang,Yuxiong; Bian,Tingzhang; Guo,Jianming

doi:10.3892/etm.2021.10401

Curcumin inhibits prostate cancer progression by regulating the miR‑30a‑5p/PCLAF axis

Authors:
- Liang Pan
- Jian Sha
- Wenyao Lin
- Yuxiong Wang
- Tingzhang Bian
- Jianming Guo
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Affiliations: Department of Urology, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200031, P.R. China, Department of Urology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China
Published online on: July 7, 2021 https://doi.org/10.3892/etm.2021.10401
Article Number: 969
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Curcumin has been shown to inhibit the growth of a variety of tumor cells. However, the biological functions of curcumin in prostate cancer (PCa) have not yet fully elucidated. The objective of the present study was to investigate the role of curcumin on the proliferation, migration, invasion and apoptosis of PCa cells and the underlying mechanism. Cell Counting Kit‑8 and flow cytometry were used to detect the effects of curcumin at different concentrations on the proliferation and apoptosis of PCa cell lines, PC‑3 and DU145. BrdU and Transwell assays, western blotting and reverse transcription‑quantitative PCR were used to determine the effect of curcumin on cell proliferation, migration and invasion, apoptosis‑related protein expression, and microRNA (miR)‑30a‑5p and PCNA clamp associated factor (PCLAF) expression, respectively. In addition, bioinformatics analysis and Pearson's correlation test were used to verify the relationship between miR‑30a‑5p and PCLAF. Curcumin was observed to impede the proliferation, migration and invasion of PCa cells, and promote their apoptosis in a time‑ and dose‑dependent manner. Curcumin enhanced miR‑30a‑5p expression and inhibited PCLAF expression; furthermore, there was a negative correlation between miR‑30a‑5p and PCLAF expression in PCa tissues. In addition, transfection of miR‑30a‑5p inhibitors partially reversed the function of curcumin on cell proliferation, migration, invasion and apoptosis. Overall, curcumin suppressed the malignant biological behaviors of PCa cells by regulating the miR‑30a‑5p/PCLAF axis.

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1	Guo Z, He C, Yang F, Qin L, Lu X and Wu J: Long non-coding RNA-NEAT1, a sponge for miR-98-5p, promotes expression of oncogene HMGA2 in prostate cancer. Biosci Rep: Sep 24, 2019 (Epub ahead of print). doi: 10.1042/BSR20190635.
2	Song Z, Zhuo Z, Ma Z, Hou C, Chen G and Xu G: Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer. Artif Cells Nanomed Biotechnol. 47:2449–2464. 2019.PubMed/NCBI View Article : Google Scholar
3	Dart DA, Koushyar S, Lanning BE and Jiang W: MiR-221 is specifically elevated in PC3 cells and its deletion reduces adhesion, motility and growth. Anticancer Res. 39:5311–5327. 2019.PubMed/NCBI View Article : Google Scholar
4	Li H, Yue L, Xu H, Li N, Li J, Zhang Z and Zhao RC: Curcumin suppresses osteogenesis by inducing miR-126a-3p and subsequently suppressing the WNT/LRP6 pathway. Aging (Albany NY). 11:6983–6998. 2019.PubMed/NCBI View Article : Google Scholar
5	Mou S, Zhou Z, He Y, Liu F and Gong L: Curcumin inhibits cell proliferation and promotes apoptosis of laryngeal cancer cells through Bcl-2 and PI3K/Akt, and by upregulating miR-15a. Oncol Lett. 14:4937–4942. 2017.PubMed/NCBI View Article : Google Scholar
6	Zhan JW, Jiao DM, Wang Y, Song J, Wu JH, Wu LJ, Chen QY and Ma SL: Integrated microRNA and gene expression profiling reveals the crucial miRNAs in curcumin anti-lung cancer cell invasion. Thorac Cancer. 8:461–470. 2017.PubMed/NCBI View Article : Google Scholar
7	Sun C, Zhang S, Liu C and Liu X: Curcumin promoted miR-34a expression and suppressed proliferation of gastric cancer cells. Cancer Biother Radiopharm. 34:634–641. 2019.PubMed/NCBI View Article : Google Scholar
8	Qian C, Wang B, Zou Y, Zhang Y, Hu X, Sun W, Xiao H, Liu H and Shi L: MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin. Cancer Manag Res. 11:6829–6840. 2019.PubMed/NCBI View Article : Google Scholar
9	Sak K: Radiosensitizing potential of curcumin in different cancer models. Nutr Cancer. 72:1276–1289. 2020.PubMed/NCBI View Article : Google Scholar
10	Xu R, Li H, Wu S, Qu J, Yuan H, Zhou Y and Lu Q: MicroRNA-1246 regulates the radio-sensitizing effect of curcumin in bladder cancer cells via activating P53. Int Urol Nephrol. 51:1771–1779. 2019.PubMed/NCBI View Article : Google Scholar
11	Dou H, Shen R, Tao J, Huang L, Shi H, Chen H, Wang Y and Wang T: Curcumin suppresses the colon cancer proliferation by inhibiting Wnt/β-catenin pathways via miR-130a. Front Pharmacol. 8(877)2017.PubMed/NCBI View Article : Google Scholar
12	Liu J, Li M, Wang Y and Luo J: Curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition. J Drug Target. 25:645–652. 2017.PubMed/NCBI View Article : Google Scholar
13	Zhao W, Zhou X, Qi G and Guo Y: Curcumin suppressed the prostate cancer by inhibiting JNK pathways via epigenetic regulation. J Biochem Mol Toxicol. 32(e22049)2018.PubMed/NCBI View Article : Google Scholar
14	Cao H, Yu H, Feng Y, Chen L and Liang F: Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis. Cancer Chemother Pharmacol. 79:985–994. 2017.PubMed/NCBI View Article : Google Scholar
15	Liu T, Chi H, Chen J, Chen C, Huang Y, Xi H, Xue J and Si Y: Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR. Gene. 631:29–38. 2017.PubMed/NCBI View Article : Google Scholar
16	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.PubMed/NCBI View Article : Google Scholar
17	Wu X, Jia R, Wang M, Chen S, Liu M, Zhu D, Zhao X, Yang Q, Wu Y, Yin Z, et al: Downregulation of microRNA-30a-5p contributes to the replication of duck enteritis virus by regulating Beclin-1-mediated autophagy. Virol J. 16(144)2019.PubMed/NCBI View Article : Google Scholar
18	Li J, Zhao LM, Zhang C, Li M, Gao B, Hu XH, Cao J and Wang GY: The lncRNA FEZF1-AS1 promotes the progression of colorectal cancer through regulating OTX1 and targeting miR-30a-5p. Oncol Res. 28:51–63. 2020.PubMed/NCBI View Article : Google Scholar
19	Noori J, Haghjooy Javanmard S and Sharifi M: The role of microRNA-30a and downstream snail1 on the growth and metastasis of melanoma tumor. Iran J Basic Med Sci. 22:534–540. 2019.PubMed/NCBI View Article : Google Scholar
20	Zhao H, Lai X, Zhang W, Zhu H, Zhang S, Wu W, Wang S, Tang M, Deng Z and Tan J: MiR-30a-5p frequently downregulated in prostate cancer inhibits cell proliferation via targeting PCLAF. Artif Cells Nanomed Biotechnol. 47:278–289. 2019.PubMed/NCBI View Article : Google Scholar
21	Yang J, Wang C, Zhang Z, Chen X, Jia Y, Wang B and Kong T: Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway. APMIS. 125:134–140. 2017.PubMed/NCBI View Article : Google Scholar
22	Sha J, Li J, Wang W, Pan L, Cheng J, Li L, Zhao H and Lin W: Curcumin induces G0/G1 arrest and apoptosis in hormone independent prostate cancer DU-145 cells by down regulating Notch signaling. Biomed Pharmacother. 84:177–184. 2016.PubMed/NCBI View Article : Google Scholar
23	Du Y, Long Q, Zhang L, Shi Y, Liu X, Li X, Guan B, Tian Y, Wang X, Li L, et al: Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling. Int J Oncol. 47:2064–2072. 2015.PubMed/NCBI View Article : Google Scholar
24	Sundram V, Chauhan SC, Ebeling M and Jaggi M: Curcumin attenuates β-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS One. 7(e35368)2012.PubMed/NCBI View Article : Google Scholar
25	Wei Q, Tu Y, Zuo L, Zhao J, Chang Z, Zou Y and Qiu J: MiR-345-3p attenuates apoptosis and inflammation caused by oxidized low-density lipoprotein by targeting TRAF6 via TAK1/p38/NF-kB signaling in endothelial cells. Life Sci. 241(117142)2020.PubMed/NCBI View Article : Google Scholar
26	Wu Z, Chen D, Wang K, Cao C and Xu X: Long non-coding RNA SNHG12 functions as a competing endogenous RNA to regulate MDM4 expression by sponging miR-129-5p in clear cell renal cell carcinoma. Front Oncol. 9(1260)2019.PubMed/NCBI View Article : Google Scholar
27	Ye J, Lei J, Fang Q, Shen Y, Xia W, Hu X, Xu Q, Yuan H, Huang J and Ni C: miR-4666-3p and miR-329 synergistically suppress the stemness of colorectal cancer cells via targeting TGF-β/Smad pathway. Front Oncol. 9(1251)2019.PubMed/NCBI View Article : Google Scholar
28	Zhang H, Li Y, Tan Y, Liu Q, Jiang S, Liu D, Chen Q and Zhang S: MiR-9-5p inhibits glioblastoma cells proliferation through directly targeting FOXP2 (Forkhead Box P2). Front Oncol. 9(1176)2019.PubMed/NCBI View Article : Google Scholar
29	Rui X, Gu TT, Pan HF, Shao SL and Shao HX: MicroRNA-381 suppresses proliferation and invasion of prostate cancer cells through downregulation of the androgen receptor. Oncol Lett. 18:2066–2072. 2019.PubMed/NCBI View Article : Google Scholar
30	Jiao DM, Yan L, Wang LS, Hu HZ, Tang XL, Chen J, Wang J, Li Y and Chen QY: Exploration of inhibitory mechanisms of curcumin in lung cancer metastasis using a miRNA- transcription factor-target gene network. PLoS One. 12(e0172470)2017.PubMed/NCBI View Article : Google Scholar
31	Yin S, Du W, Wang F, Han B, Cui Y, Yang D, Chen H, Liu D, Liu X, Zhai X, et al: MicroRNA-326 sensitizes human glioblastoma cells to curcumin via the SHH/GLI1 signaling pathway. Cancer Biol Ther. 19:260–270. 2018.PubMed/NCBI View Article : Google Scholar
32	Zhu X and Zhu R: Curcumin suppresses the progression of laryngeal squamous cell carcinoma through the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway. OncoTargets Ther. 11:3521–3531. 2018.PubMed/NCBI View Article : Google Scholar
33	Feng S, Wang Y, Zhang R, Yang G, Liang Z, Wang Z and Zhang G: Curcumin exerts its antitumor activity through regulation of miR-7/Skp2/p21 in nasopharyngeal carcinoma cells. OncoTargets Ther. 10:2377–2388. 2017.PubMed/NCBI View Article : Google Scholar
34	Zhang L, Zhang XW, Liu CH, Lu K, Huang YQ, Wang YD, Xing L, Zhang LJ, Liu N, Jiang H, et al: miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer. Mol Med Rep. 14:2077–2084. 2016.PubMed/NCBI View Article : Google Scholar
35	Zhang J, Shen C, Wang L, Ma Q, Xia P, Qi M, Yang M and Han B: Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: Involvement of the tumor suppressor miR30a and its target gene SOX4. Biochem Biophys Res Commun. 452:746–752. 2014.PubMed/NCBI View Article : Google Scholar
36	Jiang LH, Zhang HD and Tang JH: MiR-30a: A novel biomarker and potential therapeutic target for cancer. J Oncol. 2018(5167829)2018.PubMed/NCBI View Article : Google Scholar
37	Li L, Kang L, Zhao W, Feng Y, Liu W, Wang T, Mai H, Huang J, Chen S, Liang Y, et al: miR-30a-5p suppresses breast tumor growth and metastasis through inhibition of LDHA-mediated Warburg effect. Cancer Lett. 400:89–98. 2017.PubMed/NCBI View Article : Google Scholar
38	Zhu J, Zeng Y, Li W, Qin H, Lei Z, Shen D, Gu D, Huang JA and Liu Z: CD73/NT5E is a target of miR-30a-5p and plays an important role in the pathogenesis of non-small cell lung cancer. Mol Cancer. 16(34)2017.PubMed/NCBI View Article : Google Scholar
39	Zhang T, Guo J, Gu J, Chen K, Wang Z, Li H, Wang G and Wang J: KIAA0101 is a novel transcriptional target of FoxM1 and is involved in the regulation of hepatocellular carcinoma microvascular invasion by regulating epithelial-mesenchymal transition. J Cancer. 10:3501–3516. 2019.PubMed/NCBI View Article : Google Scholar
40	Abdelgawad IA, Radwan NH and Hassanein HR: KIAA0101 mRNA expression in the peripheral blood of hepatocellular carcinoma patients: Association with some clinicopathological features. Clin Biochem. 49:787–791. 2016.PubMed/NCBI View Article : Google Scholar
41	Lv W, Su B, Li Y, Geng C and Chen N: KIAA0101 inhibition suppresses cell proliferation and cell cycle progression by promoting the interaction between p53 and Sp1 in breast cancer. Biochem Biophys Res Commun. 503:600–606. 2018.PubMed/NCBI View Article : Google Scholar
42	Chen H, Xia B, Liu T, Lin M and Lou G: KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of epithelial ovarian cancer cells. Cancer Cell Int. 16(74)2016.PubMed/NCBI View Article : Google Scholar