Dataset Information

RNA interference mediated suppression of TRPV6 inhibits the progression of prostate cancer in vitro by modulating cathepsin B and MMP9 expression.

ABSTRACT:

Purpose

The transient receptor potential vanilloid 6 (TRPV6) channel is overexpressed in prostate cancer and its silencing is known to inhibit the growth of LNCaP cells. However, the role of TRPV6 in the metastasis of prostate cancer cells and its relationship to the invasive markers, matrix metalloproteinase (MMP) and cathepsin B, is unclear. Thus, the present study was focused on understanding these tumor-related processes.

Materials and methods

We performed a wound-healing assay and a Transwell migration and invasion assay to assess the migration and invasion of prostate cancer cells. Western blot analysis was used to measure the expression of cathepsin B, MMP2, and MMP9.

Results

TRPV6 siRNA significantly inhibited the proliferation of LNCaP prostate cancer cells. It also significantly attenuated the wound healing and migration capacities of LNCaP cells. Moreover, the invasiveness of LNCaP cells and the expression of MMP9 and cathepsin B in LNCaP cells were also significantly inhibited by TRPV6 siRNA.

Conclusions

The results indicate that TRPV6 may promote prostate cancer progression in association with MMP9 and cathepsin B, thereby validating further research into TRPV6 as a useful therapeutic target for local invasion or metastasis of advanced prostate cancer.

SUBMITTER: Kim DY

PROVIDER: S-EPMC8246020 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca(2+) selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage.MethodsGenomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test.ResultsWe first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage.ConclusionOur results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients are not significantly different. Although expression of trpv6 transcripts correlates with aggressive potential of prostate cancer, the TRPV6 genotype does not correlate with the onset of prostate cancer, with the Gleason score and the tumour stage.