A novel function of IMPA2, plays a tumor-promoting role in cervical cancer

Zhang, Kan; Liu, Lei; Wang, Min; Yang, Min; Li, Xianping; Xia, Xiaomeng; Tian, Jingjing; Tan, Shan; Luo, Lingli

doi:10.1038/s41419-020-2507-z

Cited by 13 publications

(15 citation statements)

References 49 publications

(62 reference statements)

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“…Thus, the development of new molecules for cervical cancer screening and treatment is urgently needed. In this study, IMPA2 was a novel gene we previously found from transcriptomics results that has been proved to be a potential tumor-promoting gene (11). And we further con rmed that IMPA2 may affect cancer cell death through inducing cell apoptosis.…”

Section: Discussionsupporting

confidence: 69%

“…Our previous study rstly showed that IMPA2 may promote the progression of cervical cancer (11). In this study, we further revealed that silenced-IMPA2 could aggravate apoptosis regulated by activating the p53signaling pathway through upregulating the expression of AIFM2, suggesting a potential therapeutic target to cervical cancer treatment.…”

Section: Introductionmentioning

confidence: 55%

“…Cervical cancer cell line SiHa (#BNCC337881) was purchased from the Cell Bank of BeNa culture collection (Beijing, China). Cervical cancer cell line HeLa (#GCC-UT0002CS) was purchased from the Cell Bank of Genechem (Shanghai, China).The IMPA2 silencing Siha and Hela cells were stably constructed as previously (11). The cells were cultured in Dulbecco's modi ed eagle medium (DMEM) (Gibco, Grand Island, NY, USA) supplemented with 10% fetal bovine serum (FBS) (Gibco, Grand Island, NY, USA) and 1% antibiotics at 37℃ in an atmosphere containing 5% CO2.…”

Section: Cells Culture and Cell Transfectionmentioning

confidence: 99%

“…Recently, Lin HY found that dysregulation of IMPA2 could promote metastatic progression of clear cell renal cell carcinoma (10). In our previous study, we have demonstrated that IMPA2 could play a tumor-promoting role in cervical cancer for the rst time (11), and the proteomic analysis results prompted that IMPA2 may regulate apoptosis process of cervical cancer, but the underlying mechanisms are still unknown.…”

Section: Introductionmentioning

confidence: 96%

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Novel Role of IMPA2 in AIFM2-Mediated Apoptosis of Cervical Cancer by Targeting p53

Liu¹,

Wang²,

Li³

et al. 2021

Preprint

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Background Cervical cancer continues to be concerned and the prognosis of locally advanced cervical cancer remains poor, which underscores pivotal needs to find novel therapeutic targets. Previously, we firstly identified Myo-inositol monophosphatase 2(IMPA2) as a potential oncogene and verified its tumor-promoting role in vitro and in vivo. In this study, we further aimed to elucidate the underlying mechanisms of IMPA2 in regulation of tumor apoptosis. Methods Cell apoptosis was assessed by apoptosis-related proteins detecting, flow cytometry, immunofluorescence and immunohistochemical staining. Fluorescence microscope was used to analyze fluorescence signal. The string database was used to find molecules regulated by IMPA2. The expression of apoptosis inducing factor mitochondria associated 2(AIFM2) was determined by qRT-PCR, western blot, immunohistochemical staining and immunofluorescence analysis. Function changes of mitochondria were evaluated by measurements of mitochondrial membrane potential and intracellular Ca2+ levels. CCK-8 assay was used to detected cell viability. Results Apoptosis of cervical cancer cells was markedly promoted when silencing IMPA2. AIFM2 was significantly up-regulated both in mRNA and protein levels, and inhibition of AIFM2 could reserve IMPA2 knockdown-induced apoptosis in a mitochondrial dependent manner. But the analysis of database and our experimental results showed that AIFM2 had little effect on cervical cancer progression and survival. Further mechanistic study revealed that IMPA2 and AIFM2 silencing apparently activated p53 and treatment of p53 inhibitor (Pifithrin α) could rescue IMPA2 knockdown-induced cell apoptosis. Conclusion Our findings displayed a novel function of IMPA2 in regulating cell apoptosis mediated by a disturbance of AIFM2 and p53 expression, potentially making it a novel therapeutic target for cervical cancer treatment.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 55%

Section: Cells Culture and Cell Transfectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Novel Role of IMPA2 in AIFM2-Mediated Apoptosis of Cervical Cancer by Targeting p53

Liu¹,

Wang²,

Li³

et al. 2021

Preprint

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“…Further examination of the individual genes within the signature revealed upregulation of chromatin regulation and DNA repair genes CDT1, NCAPD3 and EXO1. The top gene in this signature, IMPA2, has recently been reported to drive cervical cancer progression with a potential novel role in DNA repair 35 .…”

Section: Targetable Pathways Within Pnsting Low Poor Prognosis Tumorsmentioning

confidence: 99%

The clinical and molecular significance associated with STING signaling in estrogen receptor-positive early breast cancer

Parkes

Humphries

Gilmore

et al. 2020

Preprint

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STING signaling in cancer is a crucial component of response to immunotherapy and other anti-cancer treatments. Conversely, STING signaling can promote tumor invasion and metastasis. Currently, there is no robust method of measuring STING activation in cancer. Here, we describe an immunohistochemistry-based assay with digital pathology assessment of STING in tumor cells. Using this novel approach, we identify perinuclear-localized expression of STING (pnSTING) in estrogen receptor-positive (ER+) breast cancer as an independent predictor of good prognosis, associated with immune cell infiltration and upregulation of immune checkpoints. Tumors with low pnSTING are immunosuppressed with increased infiltration of “M2” -polarised macrophages. In ER-disease, pnSTING does not have a significant prognostic role, and STING appears to be uncoupled from interferon responses. Importantly, a gene signature defining low pnSTING expression in ER+ disease is predictive of poor prognosis in independent datasets. Low pnSTING is associated with chromosomal instability, MYC amplification and mTOR signaling, suggesting novel therapeutic approaches for this subgroup.

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Inositol monophosphatase 1 (IMPA1) promotes triple‐negative breast cancer progression through regulating mTOR pathway and EMT process

et al. 2022

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Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by high heterogeneity and metabolic dysregulation. Inositol monophosphatase 1(IMPA1) is critical for the metabolism of inositol, which has profound effects on gene expression and other biological processes. Here, we report for the first time that IMPA1 was upregulated in TNBC cell lines and tissues, and enhanced cell colony formation and proliferation in vitro and tumorigenicity in vivo. Additionally, IMPA1 promoted cell motility in vitro and metastatic lung colonization in vivo. Mechanistic investigations by transcriptome sequencing revealed that 4782 genes were differentially expressed between cells with IMPA1 knockdown and control cells. Among the differentially expressed genes after IMPA1 knockdown, five significantly altered genes were verified via qRT‐PCR assays. Morerover, we found that the expression profile of those five targets as a gene set was significantly associated with IMPA1 status in TNBC cells. As this gene set was associated with mTOR pathway and epithelial‐mesenchymal transition (EMT) process, we further confirmed that IMPA1 induced mTOR activity and EMT process, which at least in part contributed to IMPA1‐induced TNBC progression. Collectively, our findings reveal a previously unrecognized role of IMPA1 in TNBC progression and identify IMPA1 as a potential target for TNBC therapy.

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A novel function of IMPA2, plays a tumor-promoting role in cervical cancer

Cited by 13 publications

References 49 publications

Novel Role of IMPA2 in AIFM2-Mediated Apoptosis of Cervical Cancer by Targeting p53

Novel Role of IMPA2 in AIFM2-Mediated Apoptosis of Cervical Cancer by Targeting p53

The clinical and molecular significance associated with STING signaling in estrogen receptor-positive early breast cancer

Inositol monophosphatase 1 (IMPA1) promotes triple‐negative breast cancer progression through regulating mTOR pathway and EMT process

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