Dataset Information

Dysregulation of the miR-25-IMPA2 axis promotes metastatic progression in clear cell renal cell carcinoma.

ABSTRACT: BACKGROUND:The molecular mechanism underlying clear cell renal cell carcinoma (ccRCC) metastasis remains unclear. We therefore aimed to elucidate the role of IMPA2 in ccRCC metastatic progression. METHODS:Using the Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) staining, we investigated differences in IMPA2 mRNA and protein expression, as well as their clinical relevance, in ccRCC. To investigate the function of IMPA2 in ccRCC metastasis, we performed in vitro migration and in vivo lung colony-forming assays. We further explored the effect of microRNA (miR)-25 on IMPA2 expression by performing a luciferase reporter assay. FINDINGS:We show that ccRCC expresses relatively lower transcript levels of IMPA2 than normal kidney tissue. IMPA2 downregulation was greater in high-grade ccRCC than in low-grade ccRCC and was correlated with a poor prognosis in ccRCC patients. Importantly, we demonstrate that IMPA2 expression is inversely associated with the metastatic potential of ccRCC cells. We found that IMPA2 knockdown promotes, but overexpression suppresses, the cellular migration and lung colony-forming abilities of ccRCC cells. By using in silico and luciferase reporter assays, we found that IMPA2 expression is primarily influenced by miR-25 in ccRCC cells. Significantly, the inhibition of miR-25 function restored IMPA2 expression, thereby diminishing the metastatic potential of ccRCC cells. INTERPRETATION:We conclude that miR-25-mediated IMPA2 downregulation constitutes a novel signature for cancer metastasis and poor outcomes in ccRCC. We further postulate that the therapeutic targeting of miR-25 can be useful for preventing the metastatic progression of ccRCC associated with IMPA2 downregulation. FUND: This study was supported by the Ministry of Science and Technology, Taiwan (MOST 107-2314-B-038-094, MOST 106-2314-B-038-069-MY3, MOST 105-2320-B-038-021-MY3 and MOST 107-2320-B-038-056).

SUBMITTER: Lin YF

PROVIDER: S-EPMC6642077 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dysregulation of the miR-25-IMPA2 axis promotes metastatic progression in clear cell renal cell carcinoma.

Lin Yuh-Feng YF Chou Jian-Liang JL Chang Jeng-Shou JS Chiu I-Jen IJ Chiu Hui-Wen HW Lin Yuan-Feng YF

EBioMedicine 20190612

<h4>Background</h4>The molecular mechanism underlying clear cell renal cell carcinoma (ccRCC) metastasis remains unclear. We therefore aimed to elucidate the role of IMPA2 in ccRCC metastatic progression.<h4>Methods</h4>Using the Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) staining, we investigated differences in IMPA2 mRNA and protein expression, as well as their clinical relevance, in ccRCC. To investigate the function of IMPA2 in ccRCC metastasis, we performed in vitro ...[more]

PMID: 31202813

Similar Datasets

Project description:Clear cell renal carcinoma (ccRC) comprises a set of heterogeneous, fast-progressing pathologies with poor prognosis. Analyzing ccRC progression in terms of modifications at the molecular level may provide us with a broader understanding of the disease, paving the way for improved diagnostics and therapeutics. The role of micro-RNAs (miRs) in cancer by targeting both oncogenes and tumor suppressor genes is widely known. Despite this knowledge, the role of specific miRs and their targets in the progression of ccRC is still unknown. To evaluate the action of miRs and their target genes during ccRC progression, here we implemented a three-step method for constructing miR-gene co-expression networks for each progression stage of ccRC as well as for adjacent-normal renal tissue (NT). In the first step, we inferred all miR-gene co-expression interactions for each progression stage of ccRC and for NT. Afterwards, we filtered the whole miR-gene networks by differential gene and miR expression between successive stages: stage I with non-tumor, stage II with stage I, and so on. Finally, all miR-gene interactions whose relationships were inversely proportional (overexpressed miR and underexpressed genes and vice versa) were kept and removed otherwise. We found that miR-217 is differentially expressed in all contrasts; however, its targets were different depending on the ccRC stage. Furthermore, the target genes of miR-217 have a known role in cancer progression-for instance, in stage II network, GALNTL6 is overexpressed, and it is related to cell signaling, survival, and proliferation. In the stage III network, WNK2, a widely known tumor suppressor, is underexpressed. For the stage IV network, IGF2BP2, a post-transcriptional regulator of MYC and PTEN, is overexpressed. This data-driven network approach has allowed us to discover miRs that have different targets through ccRC progression, thus providing a method for searching possible stage-dependent therapeutic targets in this and other types of cancer.

Dataset Information

Dysregulation of the miR-25-IMPA2 axis promotes metastatic progression in clear cell renal cell carcinoma.

Publications

Dysregulation of the miR-25-IMPA2 axis promotes metastatic progression in clear cell renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets