<scp>LncRNA PSMA3‐AS1</scp> promotes cell proliferation, migration, and invasion in ovarian cancer by activating the <scp>PI3K</scp>/Akt pathway via the <scp>miR</scp>‐378a‐3p/<scp>GALNT3</scp> axis

Xu, Zhigao; Jin, Hui; Duan, Xiaoyang; Liu, Hong; Zhao, Xiwa; Fan, Shaoshuang; Wang, Yan; Yao, Tiezhu

doi:10.1002/tox.23370

Cited by 13 publications

(13 citation statements)

References 49 publications

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“…In order to develop effective drugs for OC target treatment, the study of etiology and progression mechanism at the molecular level has become the hotspot. 24 In this study, the influence of REG3A resistance. 25 In this study, REG3A knockdown reduced the DDP resistance of both OC cells and DDP resistance OC cells.…”

Section: Discussionmentioning

confidence: 92%

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REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway

Jiang,

Liu,

Liu

et al. 2023

Environmental Toxicology

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This study explored the effect of Regenerating Islet‐Derived 3‐Alpha (REG3A) on ovarian cancer (OC) progression. REG3A expression was scrutinized in clinical tissues of 97 OC cases by quantitative real‐time polymerase chain reaction (qRT‐PCR). REG3A expression in OC cells and cisplatin (DDP) resistance OC cells was regulated by transfection. LY294002 (10 μM, inhibitor of the PI3K/Akt signaling pathway) was used to treat OC cells and DDP resistance OC cells. Cell counting kit‐8 and methyl‐thiazolyl‐tetrazolium assays were applied for proliferation and DDP resistance detection. Flow cytometry was utilized for cell cycle and apoptosis analysis. The effect of REG3A on the OC cell in vivo growth was researched by establishing xenograft tumor model via using nude mice using nude mice. The expression of genes in clinical samples, cells and xenograft tumor tissues was investigated by qRT‐PCR, Western blot and immunohistochemistry. As a result, REG3A was over‐expressed in OC patients and cells, associating with dismal prognosis of patients. REG3A knockdown repressed proliferation, DDP resistance, induced cell cycle arrest and apoptosis of OC cells, and reduced the expression MDR‐1, Cyclin D1, Cleaved caspase 3 proteins and the PI3K/Akt signaling pathway activity in OC cells. LY294002 treatment abrogated the promotion effect of REG3A on OC cell proliferation, apoptosis inhibition and DDP resistance. REG3A knockdown suppressed the in vivo growth of OC cells. Thus, REG3A promoted proliferation and DDP resistance of OC cells by activating the PI3K/Akt signaling pathway. REG3A might be a promising target for the clinical treatment of OC.

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Section: Discussionmentioning

confidence: 92%

“…However, the prognosis of OC patients remains unsatisfactory. In order to develop effective drugs for OC target treatment, the study of etiology and progression mechanism at the molecular level has become the hotspot 24 . In this study, the influence of REG3A on the progression of OC was investigated.…”

Section: Discussionmentioning

confidence: 99%

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway

Jiang,

Liu,

Liu

et al. 2023

Environmental Toxicology

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“…The PI3K/AKT/mTOR signaling pathway has been shown to play an important role in the occurrence and development of OC. [30][31][32] Therefore, CBD may affect the growth of OC cells through this pathway.…”

Section: Cbd Inhibits Ovarian Cancer Cells By Regulating the Pi3k/akt...mentioning

confidence: 99%

A novel mechanism of cannabidiol in suppressing ovarian cancer through LAIR‐1 mediated mitochondrial dysfunction and apoptosis

Zhang

Liu

et al. 2023

Environmental Toxicology

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Cannabidiol (CBD) is a nonpsychoactive cannabinoid compound. It has been shown that CBD can inhibit the proliferation of ovarian cancer cells, but the underlying specific mechanism is unclear. We previously presented the first evidence for the expression of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), a member of the immunosuppressive receptor family, in ovarian cancer cells. In the present study, we investigated the mechanism by which CBD inhibits the growth of SKOV3 and CAOV3 ovarian cancer cells, and we sought to understand the concurrent role of LAIR-1. In addition to inducing ovarian cancer cell cycle arrest and promoting cell apoptosis, CBD treatment significantly affected the expression of LAIR-1 and inhibited the PI3K/AKT/mTOR signaling axis and mitochondrial respiration in ovarian cancer cells. These changes were accompanied by an increase in ROS, loss of mitochondrial membrane potential, and suppression of mitochondrial respiration and aerobic glycolysis, thereby inducing abnormal or disturbed metabolism and reducing ATP production. A combined treatment with N-acetyl-L-cysteine and CBD indicated that a reduction in ROS production would restore PI3K/AKT/mTOR pathway signaling and ovarian cancer cell proliferation. We subsequently confirmed that the inhibitory effect of CBD on the PI3K/AKT/mTOR signal axis and mitochondrial bioenergy metabolism was attenuated by knockdown of LAIR-1. Our animal studies further support the in vivo anti-tumor activity of CBD and suggest its mechanism of action. In summary, Li Ma and Huachang Zhang contributed equally to this study.

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“…This was associated with enhanced migration and invasion, which was abrogated by the addition of an EGRF inhibitor or an Akt inhibitor. Xu et al (2021) reported that upon GALNT3 knockdown in ovarian cancer cells, levels of phosphorylated PI3K and phosphorylated Akt decreased, suggesting that GALNT3 activated the PI3K/Akt pathway. Moreover, they demonstrated that the microRNA miR-378a-3p suppressed the expression of PI3K and pAkt, which could be rescued by GALNT3.…”

Section: Galnts Alter Galnac O-glycosylation Of Signal Induction Rece...mentioning

confidence: 99%

GALNTs: master regulators of metastasis-associated epithelial-mesenchymal transition (EMT)?

2022

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In humans, the UDP-N-α-D galactosamine:polypeptide N-acetylgalactosaminyltransferases family (ppGalNAc-Ts, GalNAc-Ts or GALNTs) comprises 20 isoenzymes. They are responsible for the initial synthesis of α-GalNAc1,3-O-Ser/Thr, or Tn antigen, at initiation of mucin type O-linked glycosylation. This structure is normally extended by the further sequential action of glycosytransferases to build more complex linear or branched O-linked structures, but in cancers it is frequently left unelaborated, and its presence is often associated with poor patient prognosis. Altered levels of GALNT expression or distribution have also been extensively reported in a wide range of cancers. These changes would be predicted to result in marked alterations in GalNAc O-linked glycosylation, including altered levels of site specific O-linked glycosylation and changes in the glycan structures formed, including, potentially, exposure of truncated O-glycans such as Tn antigen. Many reports have demonstrated that altered levels of specific GALNTs have prognostic significance in cancers, or shown that they are associated with changes in cell behaviour, including proliferation, migration, invasion or growth and metastasis in animal models. We have previously reviewed how deregulation of GALNTs in several epithelial cancers is a feature of different stages metastasis. Here we consider evidence that changes in GALNT expression, and therefore consequent alterations in GalNAc O-linked glycosylation, may directly influence molecules implicated in aspects of epithelial-mesenchymal transition (EMT), a fundamental aspect of cancer metastasis, during which epithelial cancer cells lose their cell–cell junctions, apical-basal polarity and adhesive interactions with basement membrane and become mesenchymal, with a spindle-shaped morphology and increased migratory capacity.

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LncRNA PSMA3‐AS1 promotes cell proliferation, migration, and invasion in ovarian cancer by activating the PI3K/Akt pathway via the miR‐378a‐3p/GALNT3 axis

Cited by 13 publications

References 49 publications

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway

A novel mechanism of cannabidiol in suppressing ovarian cancer through LAIR‐1 mediated mitochondrial dysfunction and apoptosis

GALNTs: master regulators of metastasis-associated epithelial-mesenchymal transition (EMT)?

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