RASAL1 induces to downregulate the SCD1, leading to suppression of cell proliferation in colon cancer via LXRα/SREBP1c pathway

Wang, Guangchuan; Li, Zhen; Li, Xiao; Zhang, Chunqing; Peng, Lifang

doi:10.1186/s40659-019-0268-x

Cited by 14 publications

(8 citation statements)

References 27 publications

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“…Liver X receptor α (LXRα), as a member of the nuclear receptor family, plays an important role in glucose metabolism and inflammatory response, 11 and in recent years, a study has found its important role in the development and progression of tumors. For example, one study found that regulation of the LXRα pathway could suppress the proliferation of colon cancer cells, 12 and one other study pointed out that the LXRα pathway may be related to apoptosis of BCCs promoted by 7-ketocholesterol. 11 However, there is no study on the relationship between PRMT5 and LXRα yet.…”

Section: Introductionmentioning

confidence: 99%

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

Han¹,

Wei²,

Wu³

2020

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Objective: To explore the effects of protein arginine methyltransferase 5 (PRMT5) on the biological function of breast cancer cells (BCCs) by regulating the liver X receptor α (LXRα)/NF-κBp65 pathway. Methods: A total of 80 patients with breast cancer (BC) admitted to our hospital were collected, and 80 breast cancer tissue specimens and 80 corresponding tumor-adjacent tissue specimens were sampled from them for analysis. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of PRMT5 mRNA in the sampled tissues, and the Western blot to determine the expression of LXRα and NF-κBp65 proteins in the tissues and cells. The patients were followed up to analyze their 3-year survival rate. Stable and transient overexpression vectors and inhibition vectors were constructed and transfected into BCCs. The cell counting kit-8 (CCK8), transwell, and flow cytometry were adopted to analyze the proliferation, invasion, and apoptosis of transfected cells, on which the effects of PRMT5 on LXRα and NF-κBp65 proteins were analyzed. Results: PRMT5 was highly expressed in BC patients, and LXRα was lowly expressed in them, which had a high diagnostic value. Patients with high expression of PRMT5 showed a poor prognosis, and the expression of PRMT5 was related to the tumor size, pathological stage, differentiation, and metastatic in BC patients. Overexpressed PRMT5 enhanced the cell proliferation, invasion, and glycolysis abilities, weakened apoptosis ability, further lowered expression of LXRα and increased expression of NF-κBp65, while inhibited PRMT5 caused opposite results in those aspects. Up-regulating the expression of LXRα suppressed the proliferation, invasion, and aerobic glycolysis of BCCs and promoted their apoptosis, while inhibiting it posed opposite effects. The rescue experiment revealed that down-regulating the expression of PRMT5 could counteract the promotion of downregulation of LXRα on proliferation, invasion and glycolysis of BCCs, and the nude mouse tumorigenesis test revealed that PRMT5 induced tumor on nude mice by mediating LXRα/NF-κBp65. Conclusion: Inhibition of the PRMT5 expression can accelerate apoptosis of BCCs and weaken their proliferation, invasion, and aerobic glycolysis through the LXRα/NF-κBp65 pathway.

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Section: Introductionmentioning

confidence: 99%

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

Han¹,

Wei²,

Wu³

2020

OTT

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“…26,27 It is generally believed that SREBP1 an upstream regulatory protein in the tumor lipid metabolism pathway, and most clinical studies 28 have assessed compounds that induce insulin_related genes and SREBP cleavage-activating protein, as well as affecting the synthesis of downstream cholesterol, 29,30 and even targeting ACLY as the first key substrate enzyme of DNL. 31,32 ACLY and SREBP1 are also key factors connecting glucose metabolism and lipid metabolism. 33 The significance of SREBP1 and ACLY in tumor lipid metabolism is relatively clear, and knocking down both genes aimed to refine the study of tumor lipid metabolism and find more suitable therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Biological Behavior and Lipid Metabolism of Colon Cancer Cells are Regulated by a Combination of Sterol Regulatory Element-Binding Protein 1 and ATP Citrate Lyase

Qiu

Deng

Hong

et al. 2021

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“…RASAL1(RAS protein activator like 1) is a member of the RAS GTPase-activating protein (GAP) family ( 39 ), which participates in cellular proliferation and differentiation and is associated with pulmonary fibrosis ( 40 ), and cancer ( 41 ). A recent study showed that lncRNAPCAT29 inhibits pulmonary fibrosis via downregulating RASAL1/ERK1/2 signal pathway, which suppresses the expression levels of MMP2 and MMP9 in alveolar epithelial cells and pulmonary fibroblast cell differentiation ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Survival-Associated Gene Signature in Lung Cancer Coexisting With COPD

Miao

Xiao

et al. 2021

Front. Oncol.

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Background: Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, which is associated with a worse prognosis. Thousands of biomarkers related to the survival of lung cancer have been investigated. However, those which can predict the survival of lung cancer coexisting with COPD are currently lacking. The present study aimed to identify novel gene signatures to predict the survival of patients with lung cancer coexisting COPD.Method: RNA-sequence data of lung cancer and control accompanying with matched clinical information were retrieved from the Cancer Genome Atlas (TCGA). Differently expressed genes (DEGs) associated with lung cancer coexisting COPD were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Univariate and multivariate Cox regression analyses were applied to identify survival-associated DEGs and to construct survival-associated gene signature. Kaplan-Meier survival analysis and calibration plots of the nomogram were performed to test the predictive accuracy of the gene signature. qPCR was performed to validate the genes in the prognostic signature.Results: Sequence data from 70 patients with lung cancer coexisting COPD, 127 with lung cancer alone and 108 control tissues were included for analysis. A total of 2424 DEGs were identified when comparing lung cancer coexisting COPD with controls. The biological process was primarily associated with DNA-binding transcription activator activity, peptidase inhibitor activity, endopeptidase inhibitor activity, et al. KEGG pathways were mainly enriched in neuroactive ligand-receptor interaction, cell cycle, and Staphylococcus aureus infection. A survival-associated gene signature consisting of CEACAM5, RASAL1, CSTL1, CNGB1, and SLC4A3 was identified and represented as risk score. The high-risk score group had significantly worse survival than the low-risk score group (P < 0.001). Areas under receiver operating characteristic curves were 0.943, 0.773, 0.888 for predicting overall survival at 1-, 3-, and 5-year, respectively. The risk score was an independent predictor of survival, independent of clinical factors. High conformity of the actual survival and the nomogram–predicted probability of survival by applying the risk score. Upregulation of the five genes in patients with lung cancer coexisting COPD were confirmed by qPCR in an independent cohort.Conclusion: Our study constructed and validated a novel prognostic gene signature for predicting survival of patient with lung cancer coexisting COPD, which may contribute to the clinical treatment decisions.

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RASAL1 induces to downregulate the SCD1, leading to suppression of cell proliferation in colon cancer via LXRα/SREBP1c pathway

Cited by 14 publications

References 27 publications

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

Biological Behavior and Lipid Metabolism of Colon Cancer Cells are Regulated by a Combination of Sterol Regulatory Element-Binding Protein 1 and ATP Citrate Lyase

Identification of Survival-Associated Gene Signature in Lung Cancer Coexisting With COPD

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