Effects of miR-103a-3p Targeted Regulation of TRIM66 Axis on Docetaxel Resistance and Glycolysis in Prostate Cancer Cells.

Qiang Yi,Yangzhou Li,Junfeng Wei

doi:10.3389/fgene.2021.813793

Abstract

Objective: We aimed to study the expressions of miR-103a-3p and TRIM66 in prostate cancer (PCa) cells, explore the direct target genes of miR-103a-3p, and analyze the effects of miR-103a-3p targeted regulation of the TRIM66 axis on docetaxel (DTX) resistance and glycolysis of PCa cells. Methods: Human normal prostate cells and PCa cells were used to detect the expressions of miR-103a-3p and TRIM66 and analyze their relationship. DTX-resistant (DR) PCa cells were established and transfected with miR-103a-3p and TRIM66 plasmids. The MTT assay, the plate cloning assay, the wound healing assay, and the Transwell assay were used to detect cell viability, colony formation, cell migration, and cell invasion, respectively. Cell glycolysis was analyzed using a cell glycolysis kit. Results: The expression of miR-103a-3p was low and that of TRIM66 was high in PCa cells. MiR-103a-3p had a binding site with TRIM66, and the double luciferase report confirmed that they had a targeting relationship. Compared with the PCa group cells, the DTX-resistant group cells showed increased resistance to DTX. The resistance index was 13.33, and the doubling time of the DTX-resistant group cells was significantly longer than that of the PCa group cells. The DTX-resistant group showed more obvious low expression of miR-103a-3p and high expression of TRIM66. After the DTX-resistant group cells were transfected with miR-103a-3p and TRIM66 plasmids, the expression of miR-103a-3p increased significantly and that of TRIM66 decreased significantly. Upregulation of miR-103a-3p and interference with TRIM66 can inhibit the proliferation, metastasis, and glycolysis of DTX-resistant cells. Conclusion: The expression of miR-103a-3p was downregulated and that of TRIM66 was upregulated in the malignant progression of PCa, especially during DTX resistance. Upregulation of miR-103a-3p and interference with TRIM66 can inhibit DTX resistance and glycolysis of PCa cells. Targeting TRIM66 may provide potential application value in molecular therapy for PCa.

Highlights

Prostate cancer (PCa) is one of the fatal malignant tumors and has become the second leading cause of adult male death
The expressions of miR-103a-3p and TRIM66 in PCa cells were examined in the human normal prostate epithelial cells RWPE-1 and the PCa cell PC-3 using qRT-PCR
The results showed that, compared with RWPE-1 cells, the expression of miR-103a-3p (0.39 ± 0.05) was lower and that of TRIM66 (3.21 ± 0.19) was higher in the PCa cell PC-3 (p < 0.05), as shown in Figures 1A, B

Summary

Introduction

Prostate cancer (PCa) is one of the fatal malignant tumors and has become the second leading cause of adult male death. According to the cancer statistics released by China in 2015, PCa accounted for about 2.4% of new cancers in men, including about 60,300 new cases and 26,600 deaths (Prendeville et al, 2017; Davidson et al, 2018). In 2018, PCa comprised about onefifth of the total number of new cancers in American men, with a total of about 164,649 new cases and 29,430 deaths (Abouhashem and Salah, 2020). About one-third of cases experience disease recurrence, disease progression, or eventually develop into metastatic disease after initial treatment. Cases with PCa and androgen deprivation treatment but still progressing will be diagnosed as castration-resistant PCa (CRPC) (Zhao et al, 2021)

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Conclusion