MicroRNA expression data from human renal cell cancer subtypes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Sven Wach
PROVIDER: E-GEOD-41282 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Papillary renal cell carcinomas (pRCC) are the second most common form of renal carcinoma, after clear cell Renal carcinoma (ccRCC). PRCC account for 10 to 15% of RCC and gather a heterogeneous population with no specific systemic treatment. Pathological classification by Elbe divides pRCC population in two morphologically different subtypes. Type 1 consists of predominantly basophilic cells, whereas type 2 contains mostly eosinophilic cells. Type 1 architecture corresponds with a single line of cells along the papillary axis, whereas type 2 generally exhibits several cell strata on the axis. Furthermore, type 2 cells demonstrate more aggressive characteristics, such as the presence of nucleoli and increased nuclear size. The papillary cores often contain edema fluid, foamy macrophages, and psammoma bodies. Further clinical reports identified that type I tumors are more likely to present as numerous, bilateral , indolent, low grade pRCC, whereas type II are associated with higher grade and poor prognosis related to metastatic evolution.
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Project description:Papillary renal cell carcinomas (pRCC) are the second most common form of renal carcinoma, after clear cell Renal carcinoma (ccRCC). PRCC account for 10 to 15% of RCC and gather a heterogeneous population with no specific systemic treatment. Pathological classification by Elbe divides pRCC population in two morphologically different subtypes. Type 1 consists of predominantly basophilic cells, whereas type 2 contains mostly eosinophilic cells. Type 1 architecture corresponds with a single line of cells along the papillary axis, whereas type 2 generally exhibits several cell strata on the axis. Furthermore, type 2 cells demonstrate more aggressive characteristics, such as the presence of nucleoli and increased nuclear size. The papillary cores often contain edema fluid, foamy macrophages, and psammoma bodies. Further clinical reports identified that type I tumors are more likely to present as numerous, bilateral , indolent, low grade pRCC, whereas type II are associated with higher grade and poor prognosis related to metastatic evolution. The goal of this study wad to characterize each sample in order to get an idea of the genomic profile in pRCC type 2 (pRCCII).
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Project description:Long non-coding RNA (lncRNA) play an important role in several biological processes including some renal diseases. Nevertheless, little is known on lncRNAs that are expressed in healthy kidney and involved in renal cell homeostasis and development and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs). ARPCs have been shown to be very important for renal homeostasis and repair processes thanks to their self-renewal and differentiative ability as well as their capacity to secrete different reparative factors depending on the type of damage. Through a whole genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved cell cycle and senescence biological processes. We then generated HOTAIR knock-out ARPC lines by CRISPR/Cas9 genome editing and showed that this lncRNA limits the apoptotic process of ARPCs and sustains their proliferative capacity, thus resulting responsible of their self-renewal properties. In addition, we found that the knockout of HOTAIR led to the ARPC senescence and to a significant decrease of the CD133 stem cell marker expression that is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Moreover, we found that ARPCs expressed high levels of the α-Klotho anti-aging protein and especially 2.6 fold higher levels compared to that secreted by RPTECs. The HOTAIR knockout in ARPCs leads to lower α-Klotho levels, comparable to that of RPTECs. Finnally we showed that HOTAIR induces epigenetic silencing of the cell cycle inhibitor p15 through the trimethylation of the histone H3K27. Altogether, these results shed new light on these important renal cells and may support the future development of precision therapies for kidney diseases.
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