Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences

Valentino, Anna; Calarco, Anna; Salle, Anna Di; Finicelli, Mauro; Crispi, Stefania; Calogero, Raffaele; Riccardo, Federica; Sciarra, Alessandro; Gentilucci, Alessandro; Galderisi, Umberto; Margarucci, Sabrina; Peluso, Gianfranco

doi:10.1038/onc.2017.216

Cited by 53 publications

(42 citation statements)

References 59 publications

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“…Several previous studies showed that miR-378-3p was downregulated in CRC, esophageal squamous cell carcinoma and prostate cancer (27)(28)(29). In addition, miR-378-3p has been confirmed to be downregulated in CRC compared with adjacent normal colorectal tissues (28)(29)(30), consistent with the present study, and could serve as an independent prognostic marker or potential target of novel cancer therapies. The putative binding of miR-378-3p at the 3'UTR site of LBX2 further supports the hypothesis that miR-378-3p may be an upstream regulator of LBX2 in CRC.…”

Section: Discussionsupporting

confidence: 91%

Overexpression of LBX2 associated with tumor progression and poor prognosis in colorectal cancer

Huang

Yang

et al. 2020

Oncol Lett

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Colorectal cancer (CRC) is one of the most common carcinomas with high morbidity and mortality worldwide. However, the underlying molecular mechanisms of CRC are unclear. The aim of the present study was to establish the role that overexpression of LBX2 serves in CRC and to investigate the associated biological pathways. The difference in the expression levels of LBX2 between CRC tissues and adjacent normal colorectal tissues was assessed using the Oncomine database and Tumor Immune Estimation Resource. The expression levels of LBX2 and its prognostic significance in CRC were analyzed using a t-test and χ 2 test using data from The Cancer Genome Atlas database. The Kaplan-Meier method and Cox regression analysis were used to estimate the prognostic value of LBX2 in CRC. Furthermore, the potential mechanisms of LBX2 dysregulation and its underlying molecular mechanisms in CRC were investigated using Gene Set Enrichment Analysis (GSEA). LBX2 expression levels were significantly upregulated in CRC samples compared with corresponding normal colorectal tissues (P<0.05). LBX2 upregulation was correlated with advanced tumor stage (III or IV), vascular invasion, lymphatic invasion and the male sex (all P<0.05). Kaplan-Meier analyses showed that high expression levels of LBX2 were associated with a less favorable overall survival (OS) and disease-free survival (DFS) in CRC (all P<0.05). Multivariate analyses further confirmed that LBX2 upregulation was an independent indicator of less favorable OS and DFS (all P<0.05). In addition, LBX2 DNA hypomethylation and microRNA (miR)-378a-3p downregulation correlated with LBX2 upregulation in CRC (all P<0.05). The downregulation of miR-378a-3p in CRC was also significantly associated with less favorable OS and DFS, as demonstrated using Kaplan-Meier analyses (all P<0.05). Moreover, GSEA indicated that 'VEGF signaling', 'Cell adhesion molecules CAMs', 'Toll-like receptor signaling' and 'Natural killer cell-mediated cytotoxicity' signaling pathways were enriched in the high LBX2 expressing cohort (all P<0.05). Thus, overexpression of LBX2 may be associated with the development of CRC and may serve as a novel prognostic marker and therapeutic target in CRC. The mechanisms of LBX2 upregulation in CRC are possibly associated with LBX2 DNA hypomethylation and miR-378a-3p downregulation. The potential mechanisms of LBX2 upregulation in CRC might be regulated via the 'Cell adhesion molecules CAMs', 'Toll-like receptor signaling' and 'Natural killer cell-mediated cytotoxicity' signaling pathways.

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Section: Discussionsupporting

confidence: 91%

Overexpression of LBX2 associated with tumor progression and poor prognosis in colorectal cancer

Huang

Yang

et al. 2020

Oncol Lett

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“…Research shows that miR-124-3p expression inhibits cancers such like gastric [22] and bladder cancer [23], osteosarcoma [24], and glioma [25]. Previous investigations also validated that miR-124-3p expression is downregulated in PCa [26], suggesting that high expression of circ-TRPS1 promotes the progress of PCa by adsorption of miR-124-3p.…”

Section: Discussionmentioning

confidence: 89%

Downregulation of circ-TRPS1 suppressed prostatic cancer prognoses by regulating miR-124-3p/EZH2 axis-mediated stemness

Sha

Lei

Han

et al. 2020

Preprint

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Background: Abnormal circular RNA (circRNA) expression correlates with human traits such as many kinds of cancers. Though circRNAs have links to cancer, they have less characterization in metastatic castration-resistant prostate cancer (PCa), which is main reason for PCa mortality.Methods: Therefore, high-throughput sequencing was used for selected circRNA profiles. We performed RT-qPCR to determine circ-TRPS1 expression regarding PCa tissues. We used fluorescence in situ hybridization (FISH) to detect circ-TRPS1 expression and circ-TRPS1 subcellular localization in PCa tissues. circ-TRPS1 expression in PCa cells was selectively regulated. We employed CCK8, transwell assays to monitor the cell proliferation and invasion, respectively. We employed dual-luciferase reporter and RNA pulldown assays to verify the relationship among circ-TRPS1, miR-124-3p, and EZH2. We examined the circ-TRPS1 effects on PCa cell metastasis and proliferation in vivo through a subcutaneous xenograft model as well as an intravenous tail injection model of nude mice.Results: The result showed that circ-TRPS1 was upregulated significantly in high-grade PCa tissues or cell lines. High circ-TRPS1 expression correlated to aggressive PCa phenotypes. Knockdown of circ-TRPS1 suppressed PCa proliferation and metastasis through targeting miR-124-3p/EZH2 axis-mediated stemness in PCa, which was validated by luciferase reporter assays. EZH2 overexpression or miR-124-3p inhibition reversed the inhibition of circ-TRPS1 silencing in PCa cell migration and proliferation by recovering stemness.Conclusion: In summary, data demonstrated that circ-TRPS1 suppressed PCa progression through functioning similar to a miR-124-3p sponge to enhance EZH2 expression and cancer stem-like cell differentiation. Thus, circ-TRPS1 might be a candidate target for PCa treatment.

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“…The CPT1 family constitutes the rate‐limiting step of FAO and comprises three different enzymes: CPT1A (which is present mostly in the liver), CPT1B (which is expressed mainly in the muscles), and CPT1C (mainly expressed in the brain). Overexpression of CPT1A has been shown to be associated with tumor progression in several cancer types such as breast cancer, prostate cancer, lymphoma, and leukemia . Similarly, others have shown that inhibition of this enzyme increases apoptosis and suppresses cancer cell proliferation, neovascularization, and chemoresistance .…”

Section: Multiple Myeloma and Fatty Acid Metabolismmentioning

confidence: 97%

Multiple Myeloma and Fatty Acid Metabolism

et al. 2019

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Multiple myeloma (MM) accounts for 13% to 15% of all blood cancers and is characterized by the proliferation of malignant cells within the bone marrow (BM). Despite important advances in treatment, most patients become refractory and relapse with the disease. As MM tumors grow in the BM, they disrupt hematopoiesis, create monoclonal protein spikes in the blood, initiate systemic organ and immune system shutdown, and induce painful osteolytic lesions caused by overactive osteoclasts and inhibited osteoblasts. MM cells are also extremely dependent on the BM niche, and targeting the BM niche has been clinically transformative for inhibiting the positive‐feedback “vicious cycle” between MM cells and osteoclasts that leads to bone resorption and tumor proliferation. Bone marrow adipocytes (BMAs) are dynamic, secretory cells that have complex effects on osteoblasts and tumor cells, but their role in modifying the MM cell phenotype is relatively unexplored. Given their active endocrine function, capacity for direct cell–cell communication, correlation with aging and obesity (both MM risk factors), potential roles in bone disease, and physical proximity to MM cells, it appears that BMAs support MM cells. This supposition is based on research from many laboratories, including our own. Therapeutically targeting the BMA may prove to be equally transformative in the clinic if the pathways through which BMAs affect MM cells can be determined. In this review, we discuss the potential for BMAs to provide free fatty acids to myeloma cells to support their growth and evolution. We highlight certain proteins in MM cells responsible for fatty acid uptake and oxidation and discuss the potential for therapeutically targeting fatty acid metabolism or BMAs from where they may be derived. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences

Cited by 53 publications

References 59 publications

Overexpression of LBX2 associated with tumor progression and poor prognosis in colorectal cancer

Overexpression of LBX2 associated with tumor progression and poor prognosis in colorectal cancer

Downregulation of circ-TRPS1 suppressed prostatic cancer prognoses by regulating miR-124-3p/EZH2 axis-mediated stemness

Multiple Myeloma and Fatty Acid Metabolism

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