High expression of the long non-coding RNA HEIRCC promotes Renal Cell Carcinoma metastasis by inducing epithelial-mesenchymal transition

Xiong, Jing; Liu, Ying; Luo, Shengjun; Jiang, Li; Zeng, Yang; Chen, Zhixiong; Shi, Xuefei; Lv, Bufan; Tang, Wei

doi:10.18632/oncotarget.14149

Cited by 26 publications

(22 citation statements)

References 23 publications

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“…RCC spheroids showed epithelioid characteristics and highly expressed Ca 2+ -dependent cell-cell adhesion proteins, such as E-cadherin. This result seemingly contradicts reports that stress the necessity of EMT and mesenchymal features to gain aggressive tumor features and drug resistance (6,(32)(33)(34)(35). Recently, however, several laboratories reported a more-complex relation between EMT and cancer (36).…”

Section: Discussioncontrasting

confidence: 60%

Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

et al. 2018

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Sunitinib is the standard-of-care, first-line treatment for advanced renal cell carcinoma (RCC). Characteristics of treatment-resistant RCC have been described; however, complex tumor adaptation mechanisms obstruct the identification of significant operators in resistance. We hypothesized that resistance is a late manifestation of early, treatment-induced histomolecular alterations; therefore, studying early drug response may identify drivers of resistance. We describe an epithelioid RCC growth pattern in RCC xenografts, which emerges in sunitinib-sensitive tumors and is augmented during resistance. This growth modality is molecularly and morphologically related to the RCC spheroids that advance during in vitro treatment. Based on time-lapse microscopy, mRNA and microRNA screening, and tumor behavior-related characteristics, we propose that the spheroid and adherent RCC growth patterns differentially respond to sunitinib. Gene expression analysis indicated that sunitinib promoted spheroid formation, which provided a selective survival advantage under treatment. Functional studies confirm that E-cadherin is a key contributor to the survival of RCC cells under sunitinib treatment. In summary, we suggest that sunitinib-resistant RCC cells exist in treatment-sensitive tumors and are histologically identifiable.-Lichner, Z., Saleeb, R., Butz, H., Ding, Q., Nofech-Mozes, R., Riad, S., Farag, M., Varkouhi, A. K., dos Santos, C. C., Kapus, A., Yousef, G. M. Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance.

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Section: Discussioncontrasting

confidence: 60%

Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

et al. 2018

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“…8 EMT is an important and early event in the progression of RCC, which in turn causes metastasis. 22 In the present study, we discovered that SRF is upregulated and translocated to the nucleus during RCC cell EMT. Overexpression of SRF can upregulate an important EMT regulatory factor, Snail, and facilitate 786-O cells dedifferentiation, migration and invasion.…”

Section: Discussionsupporting

confidence: 48%

Serum response factor increases renal cell carcinoma migration and invasion through promoting epithelial–mesenchymal transition

Zhao¹,

Li²,

Jiang³

et al. 2020

Int J of Urology

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Objective To explore the regulation and function of serum response factor in epithelial–mesenchymal transition in renal cell carcinoma. Methods First, bioinformatics analysis of human renal cell carcinoma tissues was carried out. Then, the expression of serum response factor, mesenchymal markers (N‐cadherin, vimentin and fibronectin) and epithelial markers (zonula occludens‐1 and epithelial cadherin) was examined in 786‐O cells (a human renal cell carcinoma cell line). Serum response factor was overexpressed with pcDNA‐serum response factor plasmid, and suppressed by CCG‐1423 (a small molecule inhibitor of serum response factor) to study how serum response factor affects epithelial–mesenchymal transition in renal cell carcinoma. A xenograft nude mouse model was established to explore whether serum response factor affected the tumorigenic ability of renal cell carcinoma cells. Results Serum response factor interacted with several important differentially expressed genes in renal cell carcinoma. In 786‐O cells, serum response factor, N‐cadherin, vimentin and fibronectin were upregulated, whereas zonula occludens‐1 and epithelial cadherin were downregulated. Serum response factor upregulation in 786‐O cells increased the Snail expression. Serum response factor suppression reduced Snail induction, and migration and invasion in renal cell carcinoma, which decreased the xenograft tumor volume. Conclusions Serum response factor is a critical transcription factor in human renal cell carcinoma. Increased serum response factor activity induces epithelial–mesenchymal transition, migration and invasion in 786‐O cells, and facilitates the progression of renal cell carcinoma. Targeting serum response factor with CCG‐1423 might be an attractive therapeutic strategy for renal cell carcinoma.

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“…Moreover, a few RCC metastasis associated lncRNAs and their mechanisms by which they affecting RCC cells invasion and metastasis have been characterized. For example, up-regulated lncRNA RCCRT1 is related with RCC patients lymph node metastasis and distant metastasis and promotes RCC cells migration and invasion [ 25 ]; increased HEIRCC promotes RCC metastasis through inducing epithelial-mesenchymal transition [ 17 ]. To identify other metastasis associated lncRNAs in RCC, we investigated the lncRNAs expression profiling associated with RCC metastasis by annotating primary RCC tumor samples and paired metastatic RCC samples microarray data.…”

Section: Discussionmentioning

confidence: 99%

“…For example, MALAT1 was highly expressed in RCC tissues and associated with reduced patient survival, while silencing of its expression inhibited RCC cell proliferation and invasion through interaction with EZH2 and miR-205 [ 15 ]. In addition, HOTAIR exerts oncogenic function in RCC cells by regulating HIF-1α/AXL signaling through inhibition of miR-217 [ 16 ]; over-expression of lncRNA HEIRCC promotes cell metastasis by inducing epithelialmesenchymal transition [ 17 ]. Although few lncRNAs function and underlying mechanisms have been characterized in RCC, the expression pattern and clinical relevance of the majority lncRNAs in RCC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

A genome-wide comprehensively analyses of long noncoding RNA profiling and metastasis associated lncRNAs in renal cell carcinoma

Xue

Shi

et al. 2017

Oncotarget

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Recently, a growing number of studies have indicated that long noncoding RNAs (lncRNAs) are emerging as new critical regulators of tumorigenesis and prognostic markers in multiple cancers. However, the expression pattern of lncRNAs and their contributions in renal cell carcinoma (RCC) remains poorly understood. In this study, we performed a genome-wide comprehensively analysis of lncRNAs profiling and clinical relevance to provide valuable lncRNA candidates for the further study in RCC. RCC and non-tumor tissues RNA sequencing data, and microarray data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), then, these data were annotated and analyzed to find dysregulated lncRNAs in RCC. We identified that hundreds of lncRNAs were differentially expressed in RCC tissues compared with normal tissues, and genomic variation analyses revealed that copy number amplification or deletion happened in some of these lncRNAs genome loci. Moreover, lots of lncRNAs expression levels are significantly associated RCC patients overall survival time, such as PVT1 and DUXAP8. Finally, we identified some novel metastasis associated lncRNAs in RCC (such as DUXAP8) by analyzing lncRNAs profiling in the RCC tissues from patients with metastasis compared with the primary RCC tissues without metastasis; knockdown of DUXAP8 could impair RCC cells invasive ability in vitro. Overall, our findings illuminate a lot of lncRNAs are aberrantly expressed in RCC that may offer useful resource for identification novel prognostic markers in this disease.

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High expression of the long non-coding RNA HEIRCC promotes Renal Cell Carcinoma metastasis by inducing epithelial-mesenchymal transition

Cited by 26 publications

References 23 publications

Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

Serum response factor increases renal cell carcinoma migration and invasion through promoting epithelial–mesenchymal transition

A genome-wide comprehensively analyses of long noncoding RNA profiling and metastasis associated lncRNAs in renal cell carcinoma

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