Diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma

Xu, G.; Lou, Ning; Xu, Yan; Shi, Hangchuan; Ruan, Hailong; Xiao, Wen; Liu, Lei; Xiao, Heng; Qiu, Bin; Bao, Lin; Yuan, Chunrong; Chen, Ke; Yang, Hongmei; Zhang, Xiaoping

doi:10.1177/1010428317699110

Cited by 13 publications

(5 citation statements)

References 29 publications

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“…S1). Previously, in two Chinese studies each encompassing about 100 patients, SR-BI protein and mRNA expression were found to be associated with the prognosis of ccRCC ( 6 , 52 ). We did not replicate this observation in our larger cohort of 172 patients.…”

Section: Discussionmentioning

confidence: 99%

Scavenger receptor BI promotes cytoplasmic accumulation of lipoproteins in clear-cell renal cell carcinoma

Velagapudi

Schraml

Yalçinkaya

et al. 2018

Journal of Lipid Research

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Clear-cell renal cell carcinomas (ccRCCs) are characterized by inactivation of the von Hippel-Lindau (VHL) gene and intracellular lipid accumulation by unknown pathomechanisms. The immunochemical analysis of 356 RCCs revealed high abundance of apoA-I and apoB, as well as scavenger receptor BI (SR-BI) in the ccRCC subtype. Given the characteristic loss of VHL function in ccRCC, we used VHL-defective and VHL-proficient cells to study the potential influence of VHL on lipoprotein uptake. VHL-defective patient-derived ccRCC cells and cell lines (786O and RCC4) showed enhanced uptake as well as less resecretion and degradation of radio-iodinated HDL and LDL (125I-HDL and 125I-LDL, respectively) compared with the VHL-proficient cells. The ccRCC cells showed enhanced vascular endothelial growth factor (VEGF) and SR-BI expression compared with normal kidney epithelial cells. Uptake of 125I-HDL and 125I-LDL by patient-derived normal kidney epithelial cells as well as the VHL-reexpressing ccRCC cell lines, 786-O-VHL and RCC4-O-VHL cells, was strongly enhanced by VEGF treatment. The knockdown of the VEGF coreceptor, neuropilin-1 (NRP1), as well as blocking of SR-BI significantly reduced the uptake of lipoproteins into ccRCC cells in vitro. LDL stimulated proliferation of 786-O cells more potently than 786-O-VHL cells in a NRP1- and SR-BI-dependent manner. In conclusion, enhanced lipoprotein uptake due to increased activities of VEGF/NRP1 and SR-BI promotes lipid accumulation and proliferation of VHL-defective ccRCC cells.

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Section: Discussionmentioning

confidence: 99%

Scavenger receptor BI promotes cytoplasmic accumulation of lipoproteins in clear-cell renal cell carcinoma

Velagapudi

Schraml

Yalçinkaya

et al. 2018

Journal of Lipid Research

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“…Experimentally, linkage of SR-B1 expression to PCa aggressiveness includes elevated expression in de novo androgenic CRPC derivatives of LNCaP (13,16), and increased tumor growth in TRAMP (21). SR-B1 also signals growth and survival of non-steroidogenic endothelial (22), and breast cancer cells (23), and association of elevated expression with aggressive characteristics and poor prognosis of breast, and clear cell renal carcinomas, indicates roles for SR-B1 in multiple malignancies (24–26).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Scavenger Receptor B1 Is Required for Steroidogenic and Nonsteroidogenic Cholesterol Metabolism in Prostate Cancer

et al. 2019

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Aberrant cholesterol metabolism is increasingly appreciated to be essential for prostate cancer (PCa) initiation and progression. Transcript expression of the high-density lipoprotein-cholesterol receptor scavenger receptor B1 (SR-B1) is elevated in primary PCa. Hypothesizing that SR-B1 expression may help facilitate malignant transformation, we document increased SR-B1 protein and transcript expression in PCa relative to normal prostate epithelium that persists in lethal castration-resistant prostate cancer (CRPC) metastasis. As intratumoral steroid synthesis from the precursor cholesterol can drive androgen receptor (AR) pathway activity in CRPC, we screened androgenic benign and cancer cell lines for sensitivity to SR-B1 antagonism. Benign cells were insensitive to SR-B1 antagonism, and cancer line sensitivity inversely correlated with expression levels of full-length and splice-variant AR. In androgen-responsive CRPC cell model C4-2, SR-B1 antagonism suppressed cholesterol uptake, de novo steroidogenesis, and AR activity. SR-B1 antagonism also suppressed growth and viability and induced endoplasmic reticulum stress and autophagy. The inability of exogenous steroids to reverse these effects indicates that AR pathway activation is insufficient to overcome cytotoxic stress caused by a decrease in the availability of cholesterol. Furthermore, SR-B1 antagonism decreased cholesterol uptake, growth, and viability of the AR-null CRPC cell model PC-3, and the small molecule SR-BI antagonist Block Lipid Transport-1 decreased xenograft growth rate despite poor pharmacologic properties. Overall, our findings show that SR-B1 is upregulated in primary and castration-resistant disease and is essential for cholesterol uptake needed to drive both steroidogenic and non-steroidogenic biogenic pathways, thus implicating SR-B1 as a novel and potentially actionable target in CRPC.

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“…The potential role of miR-1272 in ccRCC has not been researched. Scavenger receptor class B type 1 (SCARB1) has functioned as an oncogene to promote ccRCC progression [14,15]. The correlation among circ_0003146, miR-1272 and SCARB1 is fully unclear in ccRCC.…”

Section: Introductionmentioning

confidence: 99%

Circ_0003146 upregulates SCARB1 expression by acting as a miR-1272 sponge to promote malignant behaviors of clear cell renal cell carcinoma

Xia¹,

Wang

Lü³

2022

Anti-Cancer Drugs

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Circular RNAs (circRNAs) exhibit essential regulation in the malignant development of clear cell renal cell carcinoma (ccRCC). The aims of this study were to investigate the role and mechanism of circ_0003146 in the biologic behaviors of ccRCC. RNA level analysis was performed through reverse transcription-quantitative PCR assay. Cell proliferation was measured by EdU assay and cell counting kit-8 assay. The protein expression was analyzed using a western blot. Flow cytometry and caspase 3 activity assay were used to assess cell apoptosis. Cell migration and invasion were evaluated via wound healing assay and transwell assay. Circ_0003146 function in vivo was determined by xenograft tumor assay. Dual-luciferase reporter assay was applied for target relation analysis. Circ_0003146 upregulation was detected in ccRCC tissues and cells. Downregulation of circ_0003146 induced inhibition of proliferation, migration, invasion and EMT but the promotion of apoptosis in ccRCC cells. Tumor growth in vivo was inhibited after knockdown of circ_0003146. Circ_0003146 directly interacted with miR-1272, and the miR-1272 sponging effect was responsible for the function of circ_0003146. Scavenger receptor class B type 1 (SCARB1) was a target of miR-1272, and circ_0003146 regulated SCARB1 level by absorbing miR-1272. The regulation of circ_0003146 in ccRCC progression was achieved by upregulating SCARB1 in part. The current findings demonstrated that circ_0003146 contributed to the malignant progression of ccRCC via inducing SCARB1 upregulation by targeting miR-1272.

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Diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma

Cited by 13 publications

References 29 publications

Scavenger receptor BI promotes cytoplasmic accumulation of lipoproteins in clear-cell renal cell carcinoma

Scavenger receptor BI promotes cytoplasmic accumulation of lipoproteins in clear-cell renal cell carcinoma

Upregulation of Scavenger Receptor B1 Is Required for Steroidogenic and Nonsteroidogenic Cholesterol Metabolism in Prostate Cancer

Circ_0003146 upregulates SCARB1 expression by acting as a miR-1272 sponge to promote malignant behaviors of clear cell renal cell carcinoma

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