A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis

Chen, Yixin; Zhou, Yanying; Han, Fangwei; Zhao, Ying-Yuan; Tu, Meijuan; Wang, Yong Tao; Huang, Can; Fan, Shicheng; Chen, Panpan; Yao, Xinpeng; Guan, Lihuan; Yu, Ai Ming; Gonzalez, Frank J.; Huang, Min; Bi, Huichang

doi:10.7150/thno.44877

Cited by 33 publications

(43 citation statements)

References 49 publications

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“…Researchers have shown that miR-1291 inhibits esophageal squamous cell carcinoma cell proliferation and invasion through direct targeting of mucin 1 ( Luo et al, 2015 ) and prostate cancer cell proliferation and tumorigenesis by regulating the mediator of RNA polymerase II transcription subunit 1 ( Cai et al, 2019 ). We have revealed that miR-1291 suppresses multiple (proto-)oncogenes to control PC cell proliferation and tumorigenesis ( Bi et al, 2014 ; Tu et al, 2016 ; Chen et al, 2020 ). Meanwhile, miR-1291 is able to sensitize PC cells to doxorubicin therapy via the suppression of multidrug resistance-associated protein 1 ( Pan et al, 2013 ; Li et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with previous studies on miR-1291 in the regulation of ASS1 and GLUT1 using miR-1291–expressing plasmids and synthetic miR-1291 mimics ( Yamasaki et al, 2013 ; Tu et al, 2016 ), the present study demonstrated reintroduction of miR-1291 into PC cells using novel biologic miR-1291 agents effectively reduces ASS1 protein levels. Although there is an absence of miR-1291 response element within the 3′-untranslated region of ASS1, miR-1291 is able to regulate a number of transcription factors, such as Forkhead Box A2, E2F transcription factor 1, and estrogen-related receptor α ( Agarwal et al, 2015 ; Tu et al, 2019 ; Chen et al, 2020 ) that might modulate ASS1 gene expression ( Pandey et al, 2020 ), which awaits further investigation. Furthermore, it is unknown whether miR-1291 is able to regulate the expression of other enzymes involved in glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

Duan

Liu

et al. 2020

Mol Pharmacol

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Cancer cells are dysregulated and addicted to continuous supply and metabolism of nutritional glucose and amino acids (e.g., arginine) to drive the synthesis of critical macromolecules for uncontrolled growth. Recent studies have revealed that genome-derived microRNA-1291-5p (miR-1291-5p or miR-1291) may modulate the expression of argininosuccinate synthase (ASS1) and glucose transporter protein type 1 (GLUT1). We also developed a novel approach to produce recombinant miR-1291 agents for research, which are distinguished from conventional chemo-engineered miRNA mimics. Herein, we firstly demonstrated that bioengineered miR-1291 agent was selectively processed to high levels of target miR-1291-5p in human pancreatic cancer (PC) cells. Following the suppression of ASS1 protein levels, miR-1291 perturbed arginine homeostasis and preferably sensitized ASS1-abundant L3.3 cells to arginine deprivation therapy. In addition, miR-1291 treatment reduced the protein levels of GLUT1 in both AsPC-1 and PANC-1 cells, leading to a lower glucose uptake (deceased > 40%) and glycolysis capacity (reduced approximately 50%). As a result, miR-1291 largely improved cisplatin efficacy in the inhibition of PC cell viability. Our results demonstrated that miR-1291 was effective to sensitize PC cells to arginine deprivation treatment and chemotherapy through targeting ASS1-and GLUT1-mediated arginolysis and glycolysis, respectively, which may provide insights into understanding miRNA signaling underlying cancer cell metabolism and development of new strategies for the treatment of lethal PC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

Duan

Liu

et al. 2020

Mol Pharmacol

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“…For example, miR-1291 restoration repressed tumorigenesis in prostate and pancreatic xenograft tumor models via inhibition of Mediator of RNA polymerase II transcription subunit 1 (MED1) ( Cai et al, 2019 ), N-methylnicotinamide (NMN) ( Bi et al, 2014 ). In addition, miR-1291 reduced the protein levels of target genes including ATP Binding Cassette Subfamily C Member 11 (ABCC1), Forkhead box protein A2 (FOXA2), Anterior Gradient 2 (AGR2), methyl CpG binding protein 2 (MeCP2) and carnitine palmitoyltransferase 1C (CPT1C) resulting in the suppression of growth and tumorigenesis of human breast and pancreatic cell lines ( Bi et al, 2014 ; Li et al, 2015 ; Tu et al, 2016 ; Chen et al, 2020 ). Similar effects have been reported in RCC through targeting SLC2A1/GLUT1 ( Yamasaki et al, 2013 ) which it has also been reported to be overexpressed in human breast carcinomas ( da Cunha et al, 2013 ), in esophageal carcinomas by inhibiting mucin 1 (MUC1) ( Luo et al, 2015 ), whereas miR-1291 acts upstream of the Rho GTPase-activating protein 29 (ArhGAP29) to negatively regulate the RhoA/ROCK1 epithelial mesenchymal transition (EMT) pathway, ultimately leading to endometrial fibrosis ( Xu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer

et al. 2020

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Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the SLN status and the outcome of axillary lymph node dissection (ALND) in 60 patients with early breast cancer. We profiled the expression of miRNAs in paired breast tumor samples and SLNs using the NextSeq500 Illumina platform and key findings were validated by qPCR. MultiMiR Bioconductor and Reactome pathways analysis were performed to identify target genes and signaling pathways affected by altered expressed miRNAs. Our results show that nine miRNAs were differentially expressed in tumor tissues (q ≤ 0.05). In tumor samples, a 13.5-fold up-regulation of miR-7641-2 (q < 0.001) and a 2.9-fold down-regulation of miR-1291 (q < 0.001) were associated with tumors with positive SLNs. However, only down-regulation of miR-1291 (q = 0.048) remained significant in paired SLNs samples. Interestingly, a 10.5 up-regulation of miR-1291 in SLNs samples was associated with additional axillary lymph node involvement (q < 0.001). The enrichment analyses showed that canonical and non-canonical WNT pathways and negative regulation of various receptor tyrosine kinases signaling pathways were targets of miR-1291 and supports the role of miR-1291 as a tumor suppressor gene (TSG). Further studies are warranted to investigate the use of miR-1291 as a surrogate biomarker of SLN node metastasis in patients with early-stage breast cancer.

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“…Serguienko et al have demonstrated that let-7a targets SCD (stearoyl-CoA desaturase) to reduce cell proliferation and sensitivity to doxorubicin [ 42 ]. More recently, Chen et al reported that miR-1291 targets estrogen-related receptor alpha (ERR α ) to inhibit the expression level of carnitine palmitoyltransferase 1C (CPT1C), causing a decrease in cell proliferation in vitro and tumor growth in vivo [ 41 ].…”

Section: Roles Of Mitomirs In Regulating Metabolic Reprogramming Of Tnbcmentioning

confidence: 99%

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple‐Negative Breast Cancer (TNBC)

Lin

Chu

2021

Oxidative Medicine and Cellular Longevity

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Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenance, and calcium balance, leading to an emerging field of study in various cancer types, including TNBC. We herein review the recent insights into the roles and mechanism of mitomiRs in TNBC and highlight its clinical value in diagnosis and prognosis as well as vital advances on therapeutics of preclinical and clinical studies.

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A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis

Cited by 33 publications

References 49 publications

MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis

MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple‐Negative Breast Cancer (TNBC)

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