Metabolic Reprogramming by Malat1 Depletion in Prostate Cancer

Nanni, Simona; Aiello, Aurora; Salis, Chiara; Re, Agnese; Cencioni, Chiara; Bacci, Lorenza; Pierconti, Francesco; Pinto, Francesco; Ripoli, Cristian; Ostano, Paola; Baroni, Silvia; Lazzarino, Giacomo; Tavazzi, Barbara; Pugliese, Dario; Bassi, Pierfrancesco; Grassi, Claudio; Panunzi, Simona; Chiorino, Giovanna; Pontecorvi, Alfredo; Gaetano, Carlo; Farsetti, Antonella

doi:10.3390/cancers13010015

Cited by 17 publications

(27 citation statements)

References 70 publications

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“…The role of lncRNAs in tumor development and metabolism have received increasing attention [33].For example, the lncRNA MALAT1, UCA1, NBR2, etc. has been reported to regulate tumor cell metabolism, including promotes a glycolytic phenotype and increased lactate production, through regulating metabolic transcription factor, enzymes and relating pathways [34][35][36]. HIF-1α-stabilizing lncRNA (HISLA) from tumor-associated macrophages regulates aerobic glycolysis in breast cancer cells by inhibiting the hydroxylation and degradation of HIF-1α.…”

Section: Discussionmentioning

confidence: 99%

LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/ glycolysis axis in lung adenocarcinoma

Chen¹,

Hu²,

Sui³

et al. 2022

Int. J. Biol. Sci.

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Background: Lung adenocarcinoma (LUAD), the major subtype of lung cancer, is among the leading cause of cancer-related death worldwide. Energy-related metabolic reprogramming metabolism is a hallmark of cancer shared by numerous cancer types, including LUAD. Nevertheless, the functional pathways and molecular mechanism by which FAM83A-AS1 acts in metabolic reprogramming in lung adenocarcinoma have not been fully elucidated. Methods: We used transwell, wound-healing scratch assay, and metabolic assays to explore the effect of FAM83A-AS1 in LUAD cell lines. Western blotting, Co-IP assays, and ubiquitination assays were used to detect the effects of FAM83A-AS1 on HIF-1α expression, degradation, and its binding to VHL. Moreover, an in vivo subcutaneous tumor formation assay was used to detect the effect of FAM83A-AS1 on LUAD. Results: Herein, we identified FAM83A-AS1 as a metabolism-related lncRNA, which was highly correlated with glycolysis, hypoxia, and OXPHOS pathways in LUAD patients using bioinformatics analysis. In addition, we uncovered that FAM83A-AS1 could promote the migration and invasion of LUAD cells, as well as influence the stemness of LUAD cells in vivo and vitro. Moreover, FAM83A-AS1 was shown to promote glycolysis in LUAD cell lines in vitro and in vivo, and was found to influence the expression of genes related to glucose metabolism. Besides, we revealed that FAM83A-AS1 could affect glycolysis by regulating HIF-1α degradation. Finally, we found that FAM83A-AS1 knockdown could inhibit tumor growth and suppress the expression of HIF-1α and glycolysis-related genes in vivo. Conclusion:Our study demonstrates that FAM83A-AS1 contributes to LUAD proliferation and stemness via the HIF-1α/glycolysis axis, making it a potential biomarker and therapeutic target in LUAD patients.

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Section: Discussionmentioning

confidence: 99%

LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/ glycolysis axis in lung adenocarcinoma

Chen¹,

Hu²,

Sui³

et al. 2022

Int. J. Biol. Sci.

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“…Docetaxel treatment, on the other hand, may increase the generation of AR-V7 via altering the MALAT1/SF2 complex, potentially causing enzalutamide resistance [50]. Further, targeting MALAT1 was shown to change PCa cell metabolism towards a more glycolytic phenotype and to decrease the expression of oxidative phosphorylation enzymes causing cell arrest and death by Nanni et al [51]. Among others, underlying mechanisms for these effects of MALAT1 in PCa were shown to be upregulation of miR-140 [52], deregulation of miR-1 and KRAS [53], enhancing function of EZH2 [54], as well as association with estrogen receptor subunits on the chromatin level [55].…”

Section: Discussionmentioning

confidence: 99%

MALAT1 Fusions and Basal Cells Contribute to Primary Resistance against Androgen Receptor Inhibition in TRAMP Mice

Marhold

Udovica²,

Topakian

et al. 2022

Cancers

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Targeting testosterone signaling through androgen deprivation therapy (ADT) or antiandrogen treatment is the standard of care for advanced prostate cancer (PCa). Although the large majority of patients initially respond to ADT and/or androgen receptor (AR) blockade, most patients suffering from advanced PCa will experience disease progression. We sought to investigate drivers of primary resistance against antiandrogen treatment in the TRAMP mouse model, an SV-40 t-antigen driven model exhibiting aggressive variants of prostate cancer, castration resistance, and neuroendocrine differentiation upon antihormonal treatment. We isolated primary tumor cell suspensions from adult male TRAMP mice and subjected them to organoid culture. Basal and non-basal cell populations were characterized by RNA sequencing, Western blotting, and quantitative real-time PCR. Furthermore, effects of androgen withdrawal and enzalutamide treatment were studied. Basal and luminal TRAMP cells exhibited distinct molecular signatures and gave rise to organoids with distinct phenotypes. TRAMP cells exhibited primary resistance against antiandrogen treatment. This was more pronounced in basal cell-derived TRAMP organoids when compared to luminal cell-derived organoids. Furthermore, we found MALAT1 gene fusions to be drivers of antiandrogen resistance in TRAMP mice through regulation of AR. Summarizing, TRAMP tumor cells exhibited primary resistance towards androgen inhibition enhanced through basal cell function and MALAT1 gene fusions.

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“…For example, Malakar et al reported that a metabolic transcription factor, TCF7L2, is stabilized by MALAT1 and mediates the upregulation of glycolytic activity but decreases gluconeogenic enzymes via the mTORC1-4EBP1 axis [ 209 ]. Similarly, Nanni et al showed that MALAT1 silencing reduces the expression of some metabolic enzymes, including malic enzyme 3, pyruvate dehydrogenase kinases 1 and 3 and choline kinase A, which promotes a glycolytic phenotype and increased lactate production [ 210 ]. As we have described in the previous sections, the activation of glycolysis in tumor cells triggers an immunosuppressive tumor microenvironment.…”

Section: Noncoding Rnas Regulate Both Tumor Metabolism and The Immune Microenvironmentmentioning

confidence: 99%

Noncoding RNAs link metabolic reprogramming to immune microenvironment in cancers

et al. 2021

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Altered metabolic patterns in tumor cells not only meet their own growth requirements but also shape an immunosuppressive microenvironment through multiple mechanisms. Noncoding RNAs constitute approximately 60% of the transcriptional output of human cells and have been shown to regulate numerous cellular processes under developmental and pathological conditions. Given their extensive action mechanisms based on motif recognition patterns, noncoding RNAs may serve as hinges bridging metabolic activity and immune responses. Indeed, recent studies have shown that microRNAs, long noncoding RNAs and circRNAs are widely involved in tumor metabolic rewiring, immune cell infiltration and function. Hence, we summarized existing knowledge of the role of noncoding RNAs in the remodeling of tumor metabolism and the immune microenvironment, and notably, we established the TIMELnc manual, which is a free and public manual for researchers to identify pivotal lncRNAs that are simultaneously correlated with tumor metabolism and immune cell infiltration based on a bioinformatic approach.

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Metabolic Reprogramming by Malat1 Depletion in Prostate Cancer

Cited by 17 publications

References 70 publications

LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/ glycolysis axis in lung adenocarcinoma

LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/ glycolysis axis in lung adenocarcinoma

MALAT1 Fusions and Basal Cells Contribute to Primary Resistance against Androgen Receptor Inhibition in TRAMP Mice

Noncoding RNAs link metabolic reprogramming to immune microenvironment in cancers

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