Genome-wide mRNA-miRNA profiling uncovers a role of the microRNA miR-29b-1-5p/PHLPP1 signalling pathway in<i>Helicobacter pylori-</i>driven matrix metalloproteinase production in gastric epithelial cells

Datta, Chandreyee; Subuddhi, Arijita; Kumar, Manish; Lepcha, Thurbu Tshering; Chakraborty, Sohini; Jana, Kuladip; Ghosh, Zhumur; Mukhopadhyay, Asish K.; Basu, Joyoti; Kundu, Manikuntala

doi:10.1111/cmi.12859

Cited by 14 publications

(7 citation statements)

References 57 publications

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“…Gastric carcinogenesis requires genomic instabilities; however, the mechanisms of H. pylori induction of genomic instabilities remains poorly understood (Hanada et al , 2014; Koeppel et al , 2015). In this study, we extend these observations by showing that H. pylori induced an increase in the intracellular ROS levels, DNA DSBs, and DNA SSBs in the gastric cancer cell line AGS, which has been routinely used in cell culture system infected by H. pylori in vitro (Wang et al , 2016; Datta et al , 2018). To comprehensively explore the occurrence of DNA damage in the H. pylori -infected cells, we measured ROS levels, DNA damage, cell cycle checkpoint activation, and subsequent cell growth.…”

Section: Discussionsupporting

confidence: 70%

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Shi

Wang

Yanlei

et al. 2019

DNA and Cell Biology

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Helicobacter pylori is a major cause of gastric cancer. This study was aimed to explore the characteristic of DNA damage induced by H. pylori infection in gastric cancer AGS cells. After infection with H. pylori, the reactive oxygen species (ROS) levels in AGS cells were significantly higher than those in the uninfected cells. Cells with longer comet tails were detected after infection with H. pylori. The number of apurinic/apyrimidinic endonuclease 1- and phosphorylated H2AX-positive cells was significantly increased compared with the number of negative control cells. The expression of pChk1 and pChk2 was significantly upregulated by H. pylori infection. Cell growth was inhibited after H. pylori infection. All these results were dose dependent. The cell alterations were more significant upon infection with H. pylori at a multiplicity of infection (MOI) of 100:1 than at an MOI of 50:1. H. pylori infection can induce DNA single-strand breaks, DNA double-strand breaks, and cell cycle checkpoint activation after ROS generation in the gastric cancer cell line AGS, which is a potential driver for gastric cancer.

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Section: Discussionsupporting

confidence: 70%

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Shi

Wang

Yanlei

et al. 2019

DNA and Cell Biology

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“…35 Downregulation of miR-92a is associated with aggressive breast cancer features. 36 Specifically, among these identified miR-NAs, miR-29b-1-5p could upregulate Akt-dependent nuclear factor kappa B (NF-κB) signaling leading to activation of MMP2 and MMP9, 37 which had been found to play key roles in VM formation of HCC in our previous study. 1,2 Collectively, our study suggested that the miRNAs regulated by n339260 were cancerrelated miRNAs that might be involved in HCC aggressiveness.…”

Section: Discussionmentioning

confidence: 91%

Long noncoding RNA n339260 promotes vasculogenic mimicry and cancer stem cell development in hepatocellular carcinoma

et al. 2018

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Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Cancer stem cells (CSC) represent a subpopulation of tumor cells endowed with the capacity for self‐renewal and multilineage differentiation. Previous studies have indicated that CSC may participate in the formation of VM. With the advance of high‐resolution microarrays and massively parallel sequencing technology, long noncoding RNAs (lncRNAs) are suggested to play a critical role in tumorigenesis and, in particular, the development of human hepatocellular carcinoma (HCC). Currently, no definitive relationship between lncRNA and VM formation has been described. In the current study, we demonstrated that expression of the lncRNA, n339260, is associated with CSC phenotype in HCC, and n339260 level correlated with VM, metastasis, and shorter survival time in an animal model. Overexpression of n339260 in HepG2 cells was associated with a significant increase in CSC. Additionally, the appearance of VM and vascular endothelial (VE)‐cadherin, a molecular marker of VM, was also induced by n339260 overexpression. Using a short hairpin RNA approach, n339260 was silenced in tumor cells, and knockdown of n339260 was associated with reduced VM and CSC. The results of this study indicate that n339260 promotes VM, possibly by the development of CSC. The related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.

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“…PHLPP1 has been reported to be a target of miR-29b-1-5p 30 . Therefore, we investigated the role of PHLPP1 in Da0324-induced growth inhibition of GC cells.…”

Section: Resultsmentioning

confidence: 99%

“…PHLPP1 has been reported to be a direct target of miR-29b-1-5p 30 . Knockdown of miR-29b-1-5p inhibited the migration of AGS cells, knockdown of PHLPP1 increased migration rates in Helicobacter pylori-treated AGS cells 30 .…”

Section: Discussionmentioning

confidence: 99%

The Curcumin Analog Da0324 Inhibits the Proliferation of Gastric Cancer Cells via HOTAIRM1/miR-29b-1-5p/PHLPP1 Axis

Chen

et al. 2022

J. Cancer

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Background: Our previous study has shown that Da0324, a curcumin analog, exhibited significantly improved stability and antitumor activity. However, the molecular mechanisms of action of Da0324 remain poorly understood. Long non-coding RNA (lncRNA) has been shown to play a key role in tumor progression. Here, we aim to investigate the molecular mechanisms underlying the anti-cancer activity of Da0324 by regulating the lncRNA HOTAIRM1. Methods: Gastric cancer cell lines were treated with Da0324 and/or transfected with lentiviral vector expressing HOTAIRM1 shRNA, and/or miR-29b-1-5p mimics and/or small interference RNA (siRNA) against PHLPP1, or HOTAIRM1 siRNA or lentiviral vector expressing HOTAIRM1, as needed. The expression of HOTAIRM1, miR-29b-1-5p and PHLPP1 in GC cells was determined by Real-Time PCR. Cell growth was examined by CCK-8 assay and colony formation assay in vitro . The targeted relationship between HOTAIRM1 and miR-29b-1-5p was verified by luciferase reporter gene assay. PHLPP1 protein expression was examined by Western blotting. Results: Da0324 increased the expression of HOTAIRM1 in GC cells. HOTAIRM1 expression was significantly down-regulated in GC tissues, and the low expression of HOTAIRM1 was associated with the shorter survival rate of GC patients based on the TCGA database. Knockdown of HOTAIRM1 promoted GC cell proliferation whereas overexpression of HOTAIRM1 inhibited GC cell proliferation as demonstrated by CCK-8 and colony formation assays. Moreover, knockdown of HOTAIRM1 reversed the Da0324-mediated growth inhibition of GC cells. Furthermore, HOTAIRM1 acted as a sponge for miR-29b-1-5p and PHLPP1 is regulated by the HOTAIRM1/miR-29b-1-5p axis in GC cells. Overexpression of miR-29b-1-5p or knockdown of PHLPP1 reversed the ability of Da0324 to inhibit the growth of GC cells. Conclusions: Our data suggest that Da0324 exerts antitumor activity by regulating HOTAIRM1/miR-29b-1-5p/PHLPP1 axis in GC cells, and provide new insights into the anti-cancer mechanism of Da0324.

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Genome-wide mRNA-miRNA profiling uncovers a role of the microRNA miR-29b-1-5p/PHLPP1 signalling pathway inHelicobacter pylori-driven matrix metalloproteinase production in gastric epithelial cells

Cited by 14 publications

References 57 publications

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Long noncoding RNA n339260 promotes vasculogenic mimicry and cancer stem cell development in hepatocellular carcinoma

The Curcumin Analog Da0324 Inhibits the Proliferation of Gastric Cancer Cells via HOTAIRM1/miR-29b-1-5p/PHLPP1 Axis

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