Objective: To investigate the molecular mechanism by which exosomal secretion of miR-133a-3p regulates TGFBR1 and promotes the progression of prostate cancer. Methods: Exosomes were extracted from prostate cancer cells, and the expression of exosom-associated markers such as leukocyte differentiation antigen 81 (CD81) and leukocyte differentiation antigen 63 (CD63) was detected by Western blot assay (WB). The expression of miR-133a-3p was detected by miRNA matrix sequencing. Cell cloning experiment, cell proliferation 8 (CCK-8) experiment, EdU cell proliferation experiment and cell migration experiment were used to detect the effects of co-cultured exosomes+miR-133a-3p on the proliferation and metastasis of prostate cancer. Dual luciferase reporter gene assay was used to detect the binding of miR-133a-3p to TGFBR1. Real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) and WB were used to detect the effect of regulation of miR-133a-3p on transforming growth factor β receptor 1 (TGFBR1) . Results: Compared with NC group, the expressions of CD81 and CD63 in co-cultured exosomes were increased (P<0.05). Cell cloning experiment, CCK-8 experiment, EDU experiment, scratch experiment, and cell migration experiment showed that compared with NC group, the cell proliferation and metastasis ability of Mir-133a-3P group (transfected with miR-133a mimic) decreased (P<0.05). Dual luciferase reporter gene experiment showed that miR-133a-3p binding TGFBR1 sequence and overexpression of miR-133a-3p inhibited the expression of TGFBR1 (P<0.05). WB results showed that compared with NC group, the expressions of WNT, GSK3β, C-MYC and β-catenin in si-TGFBR1 group were decreased, while the expressions of WNT, GSK3β, C-MYC and β-catenin in oe-TGFBR1 group were increased (P<0.05). However, the expressions of WNT, GSK3β, C-MYC and β-catenin in oe-TGFBR1+miR-133a-3p group were not different from those in NC group. Conclusion: Prostate cancer cell-derived exosome miR-133a-3p targets TGFBR1 to promote the malignant phenotype of prostate cancer cells.
WU Hongliang
,
WANG Sheng
,
CHEN Zhijun
,
YANG Shuai
,
SUN Wenyan
,
GUAN Han
. Prostate cancer cell derived exosome miR-133a-3p promotes the malignant phenotype of protate cancer cells by targeting TGFBR1[J]. Journal of Baotou Medical College, 2025
, 41(5)
: 42
-47
.
DOI: 10.16833/j.cnki.jbmc.2025.05.008
[1] 鲁欣, 蒋栋铭, 胡明, 等. 2004-2018年全国前列腺癌死亡率的流行特征及时间趋势[J]. 上海预防医学, 2021, 33(10): 899-904, 912.
[2] Wei Y, Zhang TW, Wang BH, et al. Prospective clinical sequencing of 1016 Chinese prostate cancer patients: uncovering genomic characterization and race disparity[J]. Mol Oncol, 2023, 17(10): 2183-2199.
[3] Zhu ZJ, Zhou YJ, Li H, et al. Research trends and hotspots in prostate cancer associated exosome: a bibliometric analysis[J]. Front Oncol, 2023, 13: 1270104.
[4] Canovai M, Evangelista M, Mercatanti A, et al. Secreted miR-210-3p, miR-183-5p and miR-96-5p reduce sensitivity to docetaxel in prostate cancer cells[J]. Cell Death Discov, 2023, 9(1): 445.
[5] Zhang LS, Chen QC, Zong HT, et al. Exosome miRNA-203 promotes M1 macrophage polarization and inhibits prostate cancer tumor progression[J]. Mol Cell Biochem, 2024, 479(9): 2459-2470.
[6] Hoyos-Marulanda V, Haas CS, Goularte KL, et al. Expression of steroidogenic enzymes and TGFβ superfamily members in follicular cells of prepubertal gilts with distinct endocrine profiles[J]. Zygote, 2022, 30(1): 65-71.
[7] Lamenza FF, Ryan NM, Upadhaya P, et al. Inducible TgfbR1 and Pten deletion in a model of tongue carcinogenesis and chemoprevention[J]. Cancer Gene Ther, 2023, 30(8): 1167-1177.
[8] Wasim S, Lee SY, Kim J. Complexities of prostate cancer[J]. Int J Mol Sci, 2022, 23(22): 14257.
[9] Rebbeck TR. Prostate cancer genetics: variation by race, ethnicity, and geography[J]. Semin Radiat Oncol, 2017, 27(1): 3-10.
[10] Wang GC, Zhao D, Spring DJ, et al. Genetics and biology of prostate cancer[J]. Genes Dev, 2018, 32(17/18): 1105-1140.
[11] Schatten H. Brief overview of prostate cancer statistics, grading, diagnosis and treatment strategies[J]. Adv Exp Med Biol, 2018, 1095: 1-14.
[12] Mizuno K, Beltran H. Future directions for precision oncology in prostate cancer[J]. Prostate, 2022, 82(Suppl 1): S86-S96.
[13] Kaiser A, Haskins C, Siddiqui MM, et al. The evolving role of diet in prostate cancer risk and progression[J]. Curr Opin Oncol, 2019, 31(3): 222-229.
[14] Yang XY, Xu J, Lan SH, et al. Exosomal miR-133a-3p derived from BMSCs alleviates cerebral ischemia-reperfusion injury via targeting DAPK2[J]. Int J Nanomedicine, 2023, 18: 65-78.
[15] Wang X, Zhu LH, Lin X, et al. MiR-133a-3p inhibits the malignant progression of oesophageal cancer by targeting CDCA8[J]. J Biochem, 2022, 170(6): 689-698.