Aberrant epigenetic reprogramming represents a hallmark of renal cell carcinoma (RCC) tumorigenesis and progression. Whether there existed other epigenetic vulnerabilities that could serve as therapeutic targets remained unclear and promising. Here, we combined the clustered regularly interspaced short palindromic repeats functional screening results and multiple RCC datasets to identify JMJD6 as the potent target in RCC. JMJD6 expression correlated with poor survival outcomes of RCC patients and promoted RCC progression in vitro and in vivo. Mechanistically, aberrant p300 led to high JMJD6 expression, which activated a series of oncogenic crosstalk. Particularly, high‐throughput sequencing data revealed that JMJD6 could assemble super‐enhancers to drive a list of identity genes in kidney cancer, including VEGFA, β‐catenin, and SRC. Moreover, this JMJD6‐mediated oncogenic effect could be suppressed by a novel JMJD6 inhibitor (SKLB325), which was further demonstrated in RCC cells, patient‐derived organoid models, and in vivo. Given the probable overlapped crosstalk between JMJD6 signature and tyrosine kinase inhibitors downstream targets, targeting JMJD6 sensitized RCC to sunitinib and was synergistic when they were combined together. Collectively, this study indicated that targeting JMJD6 was an effective approach to treat RCC patients.
A planar device based on an α-In2Se3 nanoflake, in which the in-plane/out-of-plane polarization, free carriers and oxygen vacancies in SiO2 contribute to the resistive switching behavior of the device.
Tubulocystic renal cell carcinoma is a rare neoplasm of kidney with low metastatic tendency. There has only been a relatively small collection of literature dedicated to this subtype. Here we present two cases diagnosed in our center with detailed clinical information. Along with literature review, we aim to paint a comprehensive profile of TC-RCC. Hematuria and asthenia could be the chief complaints although most patients are asymptomatic. This lesion has a signature multilocular cystic form on radiology and enhancement of septa should reveal malignancy. Histologically, the cysts are lined by a single layer of flattened, cuboidal/columnar, and hobnail epithelium with enlarged nuclei and intermediate to large nucleoli. PAX8 and AMACR are most commonly positive while CD10 or CK7 could be focally stained in some cases. Overall, the diagnosis of TC-RCC should be based on comprehensive clinical and molecular results because early determination of the lesion could prelude a timely intervention and favorable prognosis.
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