Peroxisome Proliferator-activated Receptor Gamma Coactivator-1 Alpha:
A Double-edged Sword in Prostate Cancer

Zheng, Kun; Chen, Suzhen; Hu, Xiaobin

doi:10.2174/1568009622666220330194149

Cited by 12 publications

(9 citation statements)

References 157 publications

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“…Prostate cancer (PCA) is one of the most common malignant tumors in men, and its incidence has increased significantly in recent years [ 3 , 4 ]. Despite progress in its treatment, such as surgery, radiotherapy, and chemotherapy, the disease remains a challenge, particularly in cases of castrate-resistant prostate cancer [ 5 , 6 ]. Immunotherapy, which has achieved excellent therapeutic effects in various tumors, is a revolutionary breakthrough in tumor treatment [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Integrative multi-omics analysis unveils stemness-associated molecular subtypes in prostate cancer and pan-cancer: prognostic and therapeutic significance

Zheng,

Hai,

et al. 2023

J Transl Med

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Background Prostate cancer (PCA) is the fifth leading cause of cancer-related deaths worldwide, with limited treatment options in the advanced stages. The immunosuppressive tumor microenvironment (TME) of PCA results in lower sensitivity to immunotherapy. Although molecular subtyping is expected to offer important clues for precision treatment of PCA, there is currently a shortage of dependable and effective molecular typing methods available for clinical practice. Therefore, we aim to propose a novel stemness-based classification approach to guide personalized clinical treatments, including immunotherapy. Methods An integrative multi-omics analysis of PCA was performed to evaluate stemness-level heterogeneities. Unsupervised hierarchical clustering was used to classify PCAs based on stemness signature genes. To make stemness-based patient classification more clinically applicable, a stemness subtype predictor was jointly developed by using four PCA datasets and 76 machine learning algorithms. Results We identified stemness signatures of PCA comprising 18 signaling pathways, by which we classified PCA samples into three stemness subtypes via unsupervised hierarchical clustering: low stemness (LS), medium stemness (MS), and high stemness (HS) subtypes. HS patients are sensitive to androgen deprivation therapy, taxanes, and immunotherapy and have the highest stemness, malignancy, tumor mutation load (TMB) levels, worst prognosis, and immunosuppression. LS patients are sensitive to platinum-based chemotherapy but resistant to immunotherapy and have the lowest stemness, malignancy, and TMB levels, best prognosis, and the highest immune infiltration. MS patients represent an intermediate status of stemness, malignancy, and TMB levels with a moderate prognosis. We further demonstrated that these three stemness subtypes are conserved across pan-tumor. Additionally, the 9-gene stemness subtype predictor we developed has a comparable capability to 18 signaling pathways to make tumor diagnosis and to predict tumor recurrence, metastasis, progression, prognosis, and efficacy of different treatments. Conclusions The three stemness subtypes we identified have the potential to be a powerful tool for clinical tumor molecular classification in PCA and pan-cancer, and to guide the selection of immunotherapy or other sensitive treatments for tumor patients.

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Section: Introductionmentioning

confidence: 99%

Integrative multi-omics analysis unveils stemness-associated molecular subtypes in prostate cancer and pan-cancer: prognostic and therapeutic significance

Zheng,

Hai,

et al. 2023

J Transl Med

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“…Cancer cells undergo a fundamental shift in their metabolism to support increased demands for energy and biosynthetic materials, with PGC-1α standing at the crossroads of this metabolic reprogramming, regulating key pathways involved in energy production and the synthesis of macromolecules [37]. The roles of PGC-1α in mitochondrial biogenesis and function are a double-edged sword in the context of cancer [38]. On one hand, the ability of PGC-1α to enhance mitochondrial efficiency can support the energetic and biosynthetic needs of rapidly proliferating cancer cells [39].…”

Section: Discussionmentioning

confidence: 99%

High PGC-1α Expression as a Poor Prognostic Indicator in Intracranial Glioma

Cheng,

Lee,

Chang

et al. 2024

Preprint

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Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes.

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“…PPARs interact with coactivators, such as PGC-1 family: PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC) [ 91 ]. PGC-1α is a critical transcriptional coactivator involved in the regulation of mitochondrial metabolism; however, it controls various tissue-specific processes, including angiogenesis, adipogenesis, glucose metabolism, and cell survival, by interaction with transcription factors and nuclear receptors [ 92 ]. PGC-1α is involved in mRNA splicing since it possesses the characteristic RNA recognition motif and arginine/serine domain [ 91 ].…”

Section: Potential Interaction Of the Ppar Signaling Pathway And The ...mentioning

confidence: 99%

“…Similarly, the expression pattern of PGC-1α is tumor-type dependent. There is no unequivocal expression trend in melanoma since previous studies reported increased and decreased PGC1A gene expression [ 92 ]. Additionally, the role of PGC-1α in melanoma has not been fully revealed.…”

Section: Potential Interaction Of the Ppar Signaling Pathway And The ...mentioning

confidence: 99%

“…Previous studies confirmed that activation of the PGC-1α/PPAR pathway might benefit the immune response to cancer cells [ 100 ]. Additionally, it should be noted that microenvironmental conditions might modify the biological effect of the activation of PGC-1α in other types of cancer [ 92 ]. It cannot be excluded that this mechanism may also be applied to melanoma.…”

Section: Potential Interaction Of the Ppar Signaling Pathway And The ...mentioning

confidence: 99%

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PPARs and the Kynurenine Pathway in Melanoma—Potential Biological Interactions

Walczak

Gerkowicz

Krasowska

2023

IJMS

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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in various physiological and pathological processes within the skin. PPARs regulate several processes in one of the most aggressive skin cancers, melanoma, including proliferation, cell cycle, metabolic homeostasis, cell death, and metastasis. In this review, we focused not only on the biological activity of PPAR isoforms in melanoma initiation, progression, and metastasis but also on potential biological interactions between the PPAR signaling and the kynurenine pathways. The kynurenine pathway is a major pathway of tryptophan metabolism leading to nicotinamide adenine dinucleotide (NAD+) production. Importantly, various tryptophan metabolites exert biological activity toward cancer cells, including melanoma. Previous studies confirmed the functional relationship between PPAR and the kynurenine pathway in skeletal muscles. Despite the fact this interaction has not been reported in melanoma to date, some bioinformatics data and biological activity of PPAR ligands and tryptophan metabolites may suggest a potential involvement of these metabolic and signaling pathways in melanoma initiation, progression, and metastasis. Importantly, the possible relationship between the PPAR signaling pathway and the kynurenine pathway may relate not only to the direct biological effect on melanoma cells but also to the tumor microenvironment and the immune system.

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Peroxisome Proliferator-activated Receptor Gamma Coactivator-1 Alpha: A Double-edged Sword in Prostate Cancer

Cited by 12 publications

References 157 publications

Integrative multi-omics analysis unveils stemness-associated molecular subtypes in prostate cancer and pan-cancer: prognostic and therapeutic significance

Integrative multi-omics analysis unveils stemness-associated molecular subtypes in prostate cancer and pan-cancer: prognostic and therapeutic significance

High PGC-1α Expression as a Poor Prognostic Indicator in Intracranial Glioma

PPARs and the Kynurenine Pathway in Melanoma—Potential Biological Interactions

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