Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma

Cao, Qi; Ruan, Hailong; Wang, Keshan; Song, Zhengshuai; Bao, Lin; Xu, Tianbo; Xiao, Heng; Wang, Cheng; Chen, Gong; Tong, Junwei; Meng, Xiang‐Gao; Liu, Di; Yang, Hongmei; Chen, Ke; Zhang, Xiaoping

doi:10.3892/ijo.2018.4384

Cited by 51 publications

(55 citation statements)

References 44 publications

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“…Overexpression of PLIN2 has been observed in many diseases with LD accumulation. 41 In our study, data from real-time PCR showed a decrease in the mRNA level of PLIN2 after 48 hours of oxLDL treatment; however, in the same experimental group the level of PLIN2 protein was elevated.…”

Section: Discussioncontrasting

confidence: 40%

“…Interestingly, we only observed that oxLDL inhibited lipophagy by suppressing LD‐lysosome fusion and lysosomal biogenesis but not increasing lysosomal destabilization in VSMCs. Overexpression of PLIN2 has been observed in many diseases with LD accumulation . In our study, data from real‐time PCR showed a decrease in the mRNA level of PLIN2 after 48 hours of oxLDL treatment; however, in the same experimental group the level of PLIN2 protein was elevated.…”

Section: Discussionsupporting

confidence: 40%

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SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

Wang

Liu

et al. 2019

J Cellular Molecular Medi

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The formation of fat‐laden foam cells, which contributes to the fatty streaks in the plaques of atheromas, is an important process in atherosclerosis. Vascular smooth muscle cells (VSMCs) are a critical origin of foam cells. However, the mechanisms that underlie VSMC foam cell formation are not yet completely understood. Here, we demonstrated that oxidized low‐density lipoprotein (oxLDL) inhibited lipophagy by suppressing lipid droplet (LD)‐lysosome fusion and increased VSMC foam cell formation. Moreover, although oxLDL treatment inhibited lysosomal biogenesis, it had no significant effect on lysosomal proteolysis and lysosomal pH. Notably, through TMT‐based quantitative proteomic analysis and database searching, 94 differentially expressed proteins were identified, of which 54 were increased and 40 were decreased in the oxLDL group compared with those in the control group. Subsequently, SCD1, a protein of interest, was further investigated. SCD1 levels in the VSMCs were down‐regulated by exposure to oxLDL in a time‐dependent manner and the interaction between SCD1 and LDs was also disrupted by oxLDL. Importantly, SCD1 overexpression enhanced LD‐lysosome fusion, increased lysosomal biogenesis and inhibited VSMC foam cell formation by activating TFEB nuclear translocation and its reporter activity. Modulation of the SCD1/TFEB‐mediated lipophagy machinery may offer novel therapeutic approaches for the treatment of atherosclerosis.

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Section: Discussioncontrasting

confidence: 40%

Section: Discussionsupporting

confidence: 40%

SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

Wang

Liu

et al. 2019

J Cellular Molecular Medi

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“…IHC was conducted as described previously (15). Tissues were sequentially fixed in formalin, dehydrated, and embedded in paraffin.…”

Section: Ihc and Immunofluorescencementioning

confidence: 99%

Targeting the KIF4A/AR Axis to Reverse Endocrine Therapy Resistance in Castration-resistant Prostate Cancer

Cao

Song

Ruan

et al. 2020

Clinical Cancer Research

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Purpose: Emerging evidence indicates that castration-resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor (AR) or its V7 splice variant (AR-V7) and commonly becomes resistant to endocrine therapy. The aim of this work is to evaluate the function of a kinesin protein, KIF4A, in regulating AR/AR-V7 in prostate cancer endocrine therapy resistance. Experimental Design: We examined KIF4A expression in clinical prostate cancer specimens by IHC. Regulated pathways were investigated by qRT-PCR, immunoblot analysis, immunoprecipitation, and luciferase reporter and chromatin immunoprecipitation (ChIP) assays. A series of functional analyses were conducted in cell lines and xenograft models. Results: Examination of the KIF4A protein and mRNA levels in patients with prostate cancer showed that increased expression of KIF4A was positively correlated with androgen receptor (AR) levels. Patients with lower tumor KIF4A expression had improved overall survival and disease-free survival. Mechanistically, KIF4A and AR form an auto-regulatory positive feedback loop in prostate cancer: KIF4A binds AR and AR-V7 and prevents CHIP-mediated AR and AR-V7 degradation; AR binds the promoter region of KIF4A and activates its transcription. KIF4A promotes castration-sensitive and castration-resistant prostate cancer cell growth through ARand AR-V7-dependent signaling. Furthermore, KIF4A expression is upregulated in enzalutamide-resistant prostate cancer cells, and KIF4A knockdown effectively reverses enzalutamide resistance and enhances the sensitivity of CRPC cells to endocrine therapy. Conclusions: These findings indicate that KIF4A plays an important role in the progression of CRPC and serves as a crucial determinant of the resistance of CRPC to endocrine therapy.

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“…120 As described here, although several studies reported the impact of AQP-1 and PLIN2 in RCC on early detection, others showed the association of the expression of these molecules with the prognosis of advanced RCC. 121,122 Based on these reports, AQP-1 and PLIN2 are expected to be clinically useful biomarkers for RCC both in early and advanced stages in the future.…”

Section: Aqp-1 and Plin2mentioning

confidence: 99%

Current status of prognostic factors in patients with metastatic renal cell carcinoma

et al. 2019

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In recent years, the induction of novel agents, including molecular‐targeted agents and immune checkpoint inhibitors, have dramatically changed therapeutic options and their outcomes for metastatic renal cell carcinoma. Several prognostic models based on the data of patients with metastatic renal cell carcinoma treated with targeted agents or cytokine therapy have been useful in real clinical practice. Serum or peripheral blood markers related to inflammatory response have been reported to be associated with their prognosis or therapeutic efficacy. In addition to them, investigation for novel predictive factors that represent the efficacy of agents, the risk of adverse events and the prognosis are required for the advance of therapeutic strategies. The present review discusses the conventional prognostic models and clinical factors, and recent advances of the identification of some of the most promising molecules as novel biomarkers for metastatic renal cell carcinoma.

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Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma

Cited by 51 publications

References 44 publications

SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

Targeting the KIF4A/AR Axis to Reverse Endocrine Therapy Resistance in Castration-resistant Prostate Cancer

Current status of prognostic factors in patients with metastatic renal cell carcinoma

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