Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer

Zhang, Jie; Yin, De-Pei; Zhang, Yan; Zhang, Jia-nan; Yan, Yang; Zhang, Zhiqing; Zhou, Li; Lv, Yan; Huang, Haiwei; Cao, Cong

doi:10.7150/ijbs.77126

Cited by 10 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that targeted inhibition of Gαi2 in cardiomyocytes enhanced ischemic stress-induced oxidative [ 39 ]. Moreover, transcription factors binding to antioxidant response elements (ARE) could promote the transcriptional activation of Gαi2 [ 18 ]. These studies implied a potential role of Gαi2 in antioxidant response.…”

Section: Resultsmentioning

confidence: 99%

“…In osteosarcoma, overexpressed Gαi3 associated with multiple RTKs to mediate downstream Akt signaling activation, driving osteosarcoma cell growth [ 19 ]. Moreover, upregulated Gαi3 is a promising novel oncotarget of cervical cancer [ 18 ]. Gαi3 silencing or KO potently inhibited cervical cancer cell growth in vitro and in vivo [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…injected into the flanks of nude mice and pHCC1 xenografts measured after seven weeks. Gαi2 IHC staining in xenograft slides were described previously [ 18 ]. IHC intensity (“total gray”) was quantified through the Image J’s IHC Profiler.…”

Section: Methodsmentioning

confidence: 99%

“…Gαi proteins are known to associate with G protein-coupled receptors (GPCR) and to block adenylate cyclase (AC) activation, thus reducing cellular cyclic AMP (cAMP) contents [ 13 ]. Our group and others have focused on the oncogenic roles of Gαi1 and Gαi3 in different human cancers, including glioma [ 15 – 17 ], cervical cancer [ 18 ] and osteosarcoma [ 19 ]. In these cancers, overexpressed Gαi1 and Gαi3 associated with receptor tyrosine kinases (RTKs) to mediate downstream Akt-mTOR cascade activation, thereby promoting cancer cell growth in vitro and in vivo [ 15 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of G protein subunit alpha i2 as a promising therapeutic target of hepatocellular carcinoma

Chen

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a global health problem. Its incidence and mortality are increasing. Exploring novel therapeutic targets against HCC is important and urgent. We here explored the expression and potential function of Gαi2 (G protein subunit alpha i2) in HCC. The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database shows that the number of Gαi2 transcripts in HCC tissues is significantly higher than that in the normal liver tissues. Moreover, Gαi2 overexpression in HCC correlates with poor prognosis of the patients. Gαi2 mRNA and protein expression are also elevated in local HCC tissues and different human HCC cells. In patient-derived primary HCC cells and immortalized HepG2 cells, Gαi2 silencing (by targeted shRNA) or knockout (KO, by the dCas9-sgRNA method) largely suppressed cell proliferation and motility, while inducing cell cycle arrest and caspase-apoptosis activation. Moreover, Gαi2 silencing or KO-induced reactive oxygen species (ROS) production and oxidative injury in primary and HepG2 HCC cells. Whereas different antioxidants ameliorated Gαi2-shRNA-induced anti-HCC cell activity. Using a lentiviral construct, Gαi2 overexpression further augmented proliferation and motility of primary and immortalized HCC cells. Further studies revealed that the binding between the transcription factor early growth response zinc finger transcription factor 1 (EGR1) and Gαi2 DNA promoter was significantly increased in HCC tissues and cells. In vivo, intratumoral injection of Gαi2 shRNA adeno-associated virus significantly hindered HCC xenograft growth in nude mice. Moreover, the growth of Gαi2-KO HCC xenografts in the nude mice was remarkably slow. Gαi2 depletion, oxidative injury, and apoptosis induction were detected in Gαi2-silenced or Gαi2-KO HCC xenografts. Together, overexpressed Gαi2 is required for HCC cell growth in vitro and in vivo, representing as a novel and promising diagnosis marker and therapeutic target of HCC.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of G protein subunit alpha i2 as a promising therapeutic target of hepatocellular carcinoma

Chen

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…CCK-8, colony formation, “Transwell” cell migration and “Matrigel Transwell” invasion assays, were reported early 21 , 30 - 34 . The caspase activity assay, Histone DNA ELISA, nuclear TUNEL fluorescence staining and JC-1 monomer staining of mitochondrial depolarization were reported early 21 , 30 - 35 . mRNA detection by qRT-PCR and protein detection by Western blotting were reported previously 21 , 30 - 34 .…”

Section: Methodsmentioning

confidence: 99%

G protein inhibitory α subunit 2 is a molecular oncotarget of human glioma

Wang¹,

Liu²,

Wu³

et al. 2023

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

Identification of novel therapeutic oncotargets for human glioma is extremely important. Here we tested expression, potential functions and underlying mechanisms of G protein inhibitory α subunit 2 (Gαi2) in glioma. Bioinformatics analyses revealed that Gαi2 expression is significantly elevated in human glioma, correlating with poor patients' survival, higher tumor grade and wild-type IDH status. Moreover, increased Gαi2 expression was also in local glioma tissues and different glioma cells. In primary and immortalized (A172) glioma cells, Gαi2 shRNA or knockout (KO, by Cas9-sgRNA) potently suppressed viability, proliferation, and mobility, and induced apoptosis. Ectopic Gαi2 overexpression, using a lentiviral construct, further augmented malignant behaviors in glioma cells. p65 phosphorylation, NFκB activity and expression of NFκB pathway genes were decreased in Gαi2-depleted primary glioma cells, but increased following Gαi2 overexpression. There was an increased binding between Gαi2 promoter and Sp1 (specificity protein 1) transcription factor in glioma tissues and different glioma cells. In primary glioma cells Gαi2 expression was significantly reduced following Sp1 silencing, KO or inhibition. In vivo studies revealed that Gαi2 shRNA-expressing AAV intratumoral injection hindered growth of subcutaneous glioma xenografts in nude mice. Moreover, Gαi2 KO inhibited intracranial glioma xenograft in nude mice. Gαi2 depletion, NFκB inhibition and apoptosis induction were observed in subcutaneous and intracranial glioma xenografts with Gαi2 depletion. Together, overexpressed Gαi2 is important for glioma cell growth possibly by promoting NFκB cascade activation.

show abstract

Application of Repetitive Sequences in Fish Cell Depletion as a Target for the CRISPR/Cas9 System

Zhang,

Xia,

Peng

et al. 2024

Mar Biotechnol

View full text Add to dashboard Cite

Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer

Cited by 10 publications

References 35 publications

Identification of G protein subunit alpha i2 as a promising therapeutic target of hepatocellular carcinoma

Identification of G protein subunit alpha i2 as a promising therapeutic target of hepatocellular carcinoma

G protein inhibitory α subunit 2 is a molecular oncotarget of human glioma

Application of Repetitive Sequences in Fish Cell Depletion as a Target for the CRISPR/Cas9 System

Contact Info

Product

Resources

About