Cadmium and Lead Decrease Cell–Cell Aggregation and Increase Migration and Invasion in Renca Mouse Renal Cell Carcinoma Cells

Akin, Ryan; Hannibal, David; Loida, Margaret; Stevens, Emily M.; Grunz-Borgmann, Elizabeth A.; Parrish, Alan R.

doi:10.3390/ijms20246315

Cited by 9 publications

(2 citation statements)

References 55 publications

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“…Lead toxicity has also been shown to promote renal tumor formation in a large number of studies, and higher lead levels in the blood are linked with RCC [ 48 , 49 ]. Cadmium and lead induce phenotypic changes related to RCC cell aggregation, migration, and invasion [ 50 ]. GSEA analysis in our study showed that MT1X is notably involved in both hypoxia and metal ion homeostasis regulation, which are essential factors in the occurrence and progression of ccRCC.…”

Section: Discussionmentioning

confidence: 99%

MT1X is an oncogene and indicates prognosis in ccRCC

et al. 2022

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The MT1 family was previously shown to be involved in metal ion homeostasis, DNA damage, oxidative stress, and carcinogenesis. Our team’s previous study showed that MT1X is most closely associated with ccRCC. However, its role in ccRCC remains unclear. This study aimed to demonstrate MT1X’s prognostic value, potential biologic function, impact on the immune system, and influence on cell growth, the cell cycle, apoptosis, and migration in the setting of ccRCC. The relationship between clinical pathologic features and MT1X was analyzed using bioinformatics. We knocked down MT1X in the ccRCC cell line 786O with si-MT1X to verify the results of the bioinformatic analysis at the cytological level. Apoptosis assay, cell cycle assay, wound-healing assay, colony formation assay, and RT-qPCR were performed. MT1X is correlated with the stage (T and M) and grade and is able to be an independent prognostic factor for ccRCC. The TISIDB database analysis showed a significant correlation between MT1X and tumor-infiltrating lymphocytes. MT1X was also positively related to immunomodulators such as TGFB1 and CXCR4. We also found that MT1X knockdown inhibits cell growth, induces apoptosis, arrests cells in the S cell cycle, and inhibits the wound healing proportion in ccRCC. GSEA and q-PCR analysis found that downregulation of MT1X reduced the accumulation of hypoxia-associated factors. Bioinformatic analysis associated increased MT1X expression with a worse prognosis. Laboratory experiments confirmed bioinformatic findings. MT1X was also found to be an independent prognostic biomarker for ccRCC and is involved in immune system regulation.

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Section: Discussionmentioning

confidence: 99%

MT1X is an oncogene and indicates prognosis in ccRCC

et al. 2022

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“…The affinity difference between SLC39A14A and SLC39A14B for Cd 2+ is a result of alternative splicing [10]. Cd 2+ can promote cell migration and invasiveness and is reported to promote the process of RCC [34], indicating that SLC39A14B is a promoter of RCC. In short, SRSF1 promoted the alternative splicing of SLC39A14 into SLC39A14B, which aggravated RCC.…”

Section: Discussionmentioning

confidence: 99%

Circ_000829 Plays an Anticancer Role in Renal Cell Carcinoma by Suppressing SRSF1-Mediated Alternative Splicing of SLC39A14

Feng

Yang

Yaodong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Covalently closed circular RNAs (circRNAs) play critical oncogenic or anticancer roles in various cancers including renal cell carcinoma (RCC), pointing to their regulation as a promising strategy against development of RCC. We, thus, studied the tumor-suppressive role of circ_000829 in RCC through in vitro and in vivo experiments. Methods. The expression of circ_000829 was validated in clinical RCC tissues and RCC cell lines. Based on ectopic expression and knockdown experiments, we examined the interactions among circ_000829, serine and arginine rich splicing factor 1 (SRSF1), and solute carrier family 39 member 14 (SLC39A14, zinc transporter). Then, the effects of circ_000829, SRSF1, and SLC39A14 on cell cycle distribution and proliferation in vitro and on tumor growth in vivo were evaluated in RCC cells. Results. Circ_000829 was poorly expressed in RCC tissues and cells, while SRSF1 was highly expressed. Restoration of circ_000829 reduced the levels of SRSF1 and SLC39A14B, thereby repressing the RCC cell proliferation in vitro and tumor growth in vivo. Meanwhile, overexpression of SRSF1 and SLC39A14B promoted the proliferation and cell cycle entry of RCC cells. Mechanistically, circ_000829 directly bound to SRSF1, and SRSF1 enhanced the expression of SLC39A14B by mediating the alternative splicing of SLC39A14. SLC39A14B upregulation negated the effect of SLC39A14 knockdown on RCC cell proliferation. Conclusion. Hence, this study suggests the antiproliferative role of circ_000829 in RCC growth and further elucidates the underlying mechanism involving the inhibited SRSF1-mediated alternative splicing of SLC39A14 mRNA.

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