miR-21 Inhibitors Modulate Biological Functions of Gastric Cancer Cells via PTEN/PI3K/mTOR Pathway

Wang, Ping; Guan, Qunye; Zhou, Dongmei; Yu, Ze; Song, Yaobo; Qiu, Wensheng

doi:10.1089/dna.2017.3922

Cited by 45 publications

(37 citation statements)

References 24 publications

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“…Previous studies demonstrated that miR-21-5p plays a tumor-promoting role in many types of cancer. It functions by regulating several oncogenic pathways such as PI3K/AKT and modulating matrix metalloproteases (25,26). Consistently, we found that miR-21-5p was upregulated in gastric cancer tissues and miR-21-5p expression was associated with tumor grade, and exhibited high expression in high-grade tumors and low expression in low-grade tumors.…”

Section: Discussionsupporting

confidence: 77%

miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer

Liu

Fei

et al. 2018

Oncol Rep

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Pyruvate dehydrogenase A1 (PDHA1) is a component of the pyruvate dehydrogenase enzyme complex, which links glycolysis and the tricarboxylic acid cycle, and is important for cancer metabolism shift. PDHA1 downregulation has been revealed in several types of cancer to enhance glycolysis. However, the role of PDHA1 in gastric cancer remains largely unknown. In the present study, we found that PDHA1 was significantly downregulated in gastric cancer, and associated with poor prognosis. PDHA1 downregulation promoted gastric cancer glycolysis and cancer progression. miR‑21‑5p directly targeted PDHA1 to suppress PDHA1 expression, and promote glycolysis as well as cell proliferation in gastric cancer. Moreover, miR‑21‑5p was significantly upregulated in gastric cancer and negatively associated with PDHA1 expression in gastric cancer samples. Our results indicated that miR‑21‑5p targeted PDHA1 to regulate a metabolic switch and cancer progression in gastric cancer, and reveal the potential role of the miR‑21‑5p/PDHA1 axis in gastric cancer treatment.

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Section: Discussionsupporting

confidence: 77%

miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer

Liu

Fei

et al. 2018

Oncol Rep

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“…RECK, reversion-inducing-cysteine-rich protein with kazal motifs; SP1, specificity protein 1; TSC1, tuberous sclerosis 1; VEGFA, vascular endothelial growth factor A. migration of GC cells by directly binding to the 3'-UTR of PTEN. Whereas antisense oligonucleotides against miR-21 were able to increase PTEN expression and impair downstream PI3K/Akt/mTOR signaling, leading to reverse effects on these biological behaviors of GC cells (27,69). In addition, miR-21 was involved in the regulation of a number of Polycomb group (PcG) proteins on gastric cancer stem cells (CSCs), a small subset of cancer cells with self-renewal and tumor-initiating properties, which are critical in tumor metastasis, recurrence and chemoresistance (70).…”

Section: Pten Mediates Oncogenic Activities Of Mirnas Via Pi3k/akt Simentioning

confidence: 99%

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review)

Zhu

Xiong

et al. 2019

Oncol Rep

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Gastric carcinogenesis arises from complicated interactions among host, environmental and bacterial factors, which cause genetic and epigenetic dysregulation of oncogenic and tumor-suppressive genes. MicroRNAs (miRNAs), a class of small non-coding RNAs that post-transcriptionally regulate ~30% human genes, may serve as oncogenes or tumor-suppressors in malignancies, including gastric cancer (GC). Although miRNA dysregulation commonly exists in GC, exact roles miRNAs serve in the pathogenesis and promotion of this tumor remain undetermined. Recently, results of previous studies regarding mechanisms underlying miRNAs generally converged on pathways critical in cellular processes, including cell proliferation, apoptosis and invasion, among which phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling is a fundamental one, with frequent oncogenic alterations in GC. Therefore, in the present review, the disorder and function of miRNAs and PTEN/PI3K/Akt signaling in GC are discussed. Additionally, how miRNAs transduce their effects by regulating this pathway, particularly in GC stem cells and the tumor microenvironment, and two novel hypotheses significant in carcinogenesis, tumor progression and recurrence, are discussed. Furthermore, the roles of miRNAs and the PTEN/PI3K/Akt pathway in target therapies against this lethal disease are outlined.

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“…MiR-21, miR-450 and miR-149 participating in the regulation of glaucoma have been reported [14]. Moreover, miR-21 and miR-149 are associated with the development of gastric cancer [12,13]. More importantly, given the glaucoma exhibited similar cancer type with gastric cancer, hence, we explored the roles of miR-450 in gastric cancer and miR-450 was con rmed to be a tumor suppressor in gastric cancer.…”

Section: Discussionmentioning

confidence: 98%

“…MiR-582-5p inhibits cell proliferation and promoted apoptosis by regulating AKT3 [6]. Other studies have also shown the inhibitory effect of miRNAs on the progression and development of gastric cancer, including miR-744, miR-140-5p, miR-181a, miR-182, miR-802, miR-21, miR-149 [7][8][9][10][11][12][13]. On the other hand, miR-450, as a novel miRNA, which function as a tumor suppressor in the regulation of glaucoma [14].…”

Section: Introductionmentioning

confidence: 99%

MiR-450 inhibits cell proliferation, migration and invasion and induces apoptosis in gastric cancer via targeting CREB1

Zhao¹,

Zhang²,

Y³

et al. 2020

Preprint

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Background：Gastric cancer seriously affects human health and research on gastric cancer is increasing. In recent years, molecular targets are hot research topics. We aimed to explore the effects and mechanisms of miR-450 on the development and progression of gastric cancer.Methods：We used gain-of-function approaches to investigate the gastric cancer cell proliferation, apoptosis, migration and invasion, including, RT-qPCR, CCK-8, colony formation, flow cytometry, western blot, wound healing, transwell chamber, HE, TUNEL, dual luciferase reporter and tumor formation analysis.Results：We found that the expression levels of miR-450 were greatly decreased in gastric cancer cells and overexpression of miR-450 inhibited the gastric cancer cell proliferation, migration and invasion, while induced apoptosis in gastric cancer in vitro. Moreover, we demonstrated that ectopic expression of miR-450 inhibited tumor growth in vivo. At the molecular level, overexpression of miR-450 significantly increased the expression levels of apoptosis-associated proteins, including Caspase-3, Caspase-9 and BAX, while inhibited the expression level of Bcl-2. Mechanically, luciferase reporter experiment suggested that CREB1 had a negative correlation with miR-450 expression and knockdown of CREB1 alleviated gastric cancer. Furthermore, we also found that miR-450 inhibited the activation of AKT/GSK-3β signaling pathway to inhibit the progression of gastric cancer.Conclusions：miR-450 repressed gastric cancer cell proliferation, migration and invasion and induced apoptosis through targeting CREB1 by modulating AKT/GSK-3β signaling pathway, which may provide a new molecular target for the treatment of gastric cancer.

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miR-21 Inhibitors Modulate Biological Functions of Gastric Cancer Cells via PTEN/PI3K/mTOR Pathway

Cited by 45 publications

References 24 publications

miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer

miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review)

MiR-450 inhibits cell proliferation, migration and invasion and induces apoptosis in gastric cancer via targeting CREB1

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