SphK1 promotes development of non‑small cell lung cancer through activation of STAT3

Ma, Yuefeng; Xing, Xin; Kong, Ranran; Cheng, Chuantao; Li, Suoni; Yang, Xiaoping; Li, Shaomin; Zhao, Feng; Sun, Liangzhang; Cao, Gang

doi:10.3892/ijmm.2020.4796

Cited by 24 publications

(26 citation statements)

References 50 publications

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“…Notably, SphK1 promotes NSCLC development. Overexpression of SphK1 exacerbates the development of NSCLC by activating STAT3 [ 21 , 42–48 ]. Herein, LINC00960 sponged miR-124a to upregulate the expression of SphK1.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Long non-coding RNA 00960 promoted the aggressiveness of lung adenocarcinoma via the miR-124a/SphK1 axis

et al. 2022

Bioengineered

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Long non-coding RNAs (lncRNAs) are closely associated with the development of lung adenocarcinoma (LADC). The present study focused on the role of LINC00960 in LADC. miRNA and mRNA expression levels were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cellular functions were evaluated by MTT, colony formation, and Transwell assays, respectively. LINC00960 Luciferase and RNA pull-down assays were performed to clarify the interaction between miR-124a and LINC00960 or Recombinant Sphingosine Kinase 1 (SphK1). We observed that LINC00960 was overexpressed in LADC tumor tissues and cell lines. LINC00960 knockdown suppressed the proliferation, migration, and invasion of LADC cells. Moreover, LINC00960 sponged miR-124a to inhibit the SphK1/S1P pathway in LADC cells. LINC00960 knockdown markedly reduced the rate of tumor growth. The luciferase reporter assay results demonstrated an interaction between miR-124a and LINC00960 or SphK1. This interaction was confirmed using the RNA pull-down assay. In addition, miR-124a downregulation or SphK1 upregulation reversed the inhibitory effects of LINC00960 knockdown on cellular functions of LADC cells, suggesting that LINC00960 may be a potential therapeutic biomarker for LADC via the miR-124a/SphK1 axis. Accordingly, LINC00960 may be a potential therapeutic biomarker for LADC.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Long non-coding RNA 00960 promoted the aggressiveness of lung adenocarcinoma via the miR-124a/SphK1 axis

et al. 2022

Bioengineered

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“…SphK1 is therefore a potential oncotarget of NSCLC ( 38 , 39 ). Ma et al reported that SphK1 mediated signal transducer and activator of transcription 3 (STAT3) while promoting NSCLC cell proliferation and migration ( 47 ). In addition, Ni et al, showed that SphK1 is important for epithelial mesenchymal transition (EMT) in A549 cells ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620

Zha

Xia

et al. 2021

Front. Oncol.

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In non-small-cell lung carcinoma (NSCLC), aberrant activation of mammalian target of rapamycin (mTOR) contributes to tumorigenesis and cancer progression. PQR620 is a novel and highly-potent mTOR kinase inhibitor. We here tested its potential activity in NSCLC cells. In primary human NSCLC cells and established cell lines (A549 and NCI-H1944), PQR620 inhibited cell growth, proliferation, and cell cycle progression, as well as cell migration and invasion, while inducing significant apoptosis activation. PQR620 disrupted assembles of mTOR complex 1 (mTOR-Raptor) and mTOR complex 2 (mTOR-Rictor-Sin1), and blocked Akt, S6K1, and S6 phosphorylations in NSCLC cells. Restoring Akt-mTOR activation by a constitutively-active Akt1 (S473D) only partially inhibited PQR620-induced cytotoxicity in NSCLC cells. PQR620 was yet cytotoxic in Akt1/2-silenced NSCLC cells, supporting the existence of Akt-mTOR-independent mechanisms. Indeed, PQR620 induced sphingosine kinase 1 (SphK1) inhibition, ceramide production and oxidative stress in primary NSCLC cells. In vivo studies demonstrated that daily oral administration of a single dose of PQR620 potently inhibited primary NSCLC xenograft growth in severe combined immune deficient mice. In PQR620-treated xenograft tissues, Akt-mTOR inactivation, apoptosis induction, SphK1 inhibition and oxidative stress were detected. In conclusion, PQR620 exerted potent anti-NSCLC cell activity via mTOR-dependent and -independent mechanisms.

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“…In breast cancer-bearing mice, targeted inhibition of SPHK1 signaling could reduce obesityrelated in ammation, S1P signal transduction, and lung metastasis and prolong survival. Additionally, several studies have shown that SPHK1 catalyzes the formation of S1P and promotes tumor cell proliferation, migration, invasion, and EMT [33]. ST3GAL4 encodes for β-galactosidase-α 2,3sialyltransferase 4, showing involvement in the biosynthesis of tumor antigens sulfo-sLe (x) and sLe (x).…”

Section: Discussionmentioning

confidence: 99%

Novel Lipid Metabolism-Related Gene Signature in Lung Adenocarcinoma Patients Experiencing Lymph Node Metastasis

Lao

Chen

Xiong

et al. 2022

Preprint

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Accumulating evidence revealed that lipid metabolic reprogramming facilitates lymph node metastasis and cancer progression. This study aimed to perform comprehensive bioinformatic analyses of the lipid metabolism-related impact in lung adenocarcinoma (LUAD) patients experiencing lymph node metastasis (LNM). Clinicopathological information and RNA-sequence data on LUAD patients were collected from the TCGA and GEO databases. Subsequently, 189 differentially expressed lipid metabolism-related genes (LMRGs) were screened for LUAD patients with and without LNM. Based on the risk scoring system related to prognosis, we further correlated the LMRGs with diverse clinicopathological outcomes, genomic alterations, and immune features, as well as immunotherapeutic responses and drug susceptibility. A three-gene lipid metabolic signature (GPD1L, SPHK1, and ST3GAL4) associated with tumor progression in LUAD with LNM was identified. Analyses revealed that the high-risk group had worse overall survival; an increased proportion of M0 macrophages and degranulating mast cell infiltration; increased non-responders to immunotherapy; and resistance to several common TKI drugs. Interestingly, we also found that high-risk patients had higher tumor mutation burdens and PDL-1 expression, suggesting that this subset of patients may benefit from immunotherapy plus LMRG-targeted therapy. Additionally, the results showed that the differential expressed genes (DEGs) of the high-risk group were enriched in the REACTIVE OXYGEN SPECIES pathway. Overall, we identify a lipid metabolic signature that has prognostic value and provides new insights into molecular mechanisms and precision therapies of lipid metabolism-related LUAD regional metastasis.

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SphK1 promotes development of non‑small cell lung cancer through activation of STAT3

Cited by 24 publications

References 50 publications

RETRACTED ARTICLE: Long non-coding RNA 00960 promoted the aggressiveness of lung adenocarcinoma via the miR-124a/SphK1 axis

RETRACTED ARTICLE: Long non-coding RNA 00960 promoted the aggressiveness of lung adenocarcinoma via the miR-124a/SphK1 axis

The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620

Novel Lipid Metabolism-Related Gene Signature in Lung Adenocarcinoma Patients Experiencing Lymph Node Metastasis

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