<i>Helicobacter pylori</i>‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

Shao, Liu-Jia-Zi; Chen, Zheng; Soutto, Mohammed; Zhu, Shoumin; Lu, Heng; Romero–Gallo, Judith; Peek, Richard M.; Zhang, Shutian; El–Rifai, Wael

doi:10.1096/fj.201701456rr

Cited by 63 publications

(43 citation statements)

References 57 publications

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“…Helicobacter pylori has been acknowledged to be one of the most important pathogenic factors for GC [42]. It has also been reported that H. pylori can regulate CDDP resistance [43,44]. Nevertheless, many of the patients did not receive H. pylori examination, so we did not analyze the relationship between H. pylori and circMCTP2.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA MCTP2 Inhibits Cisplatin Resistance in Gastric Cancer by miR-99a-5p-Mediated Induction of MTMR3 Expression

Sun

et al. 2020

Preprint

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Background: Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). Poor prognosis of GC patients is partially due to development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of non-coding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated. Methods: RNA-sequencing was used to identify the differentially expressed circRNAs between the CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and Luciferase reporter assays were performed to confirm the interaction among circMCTP2, miR-99a-5p, and myotubularin related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM).Results: CircMCTP2 was found to be downregulated in the CDDP-resistant GC cells and tissues as compared to that of the CDDP-sensitive ones. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited cell proliferation and autophagy while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 upregulated MTMR3 by sponging miR-99a-5p, and knockdown of MTMR3 could reverse the effects of circMCTP2 on CDDP resistance and autophagy of GC cells. Conclusions: CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.

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Section: Discussionmentioning

confidence: 99%

Circular RNA MCTP2 Inhibits Cisplatin Resistance in Gastric Cancer by miR-99a-5p-Mediated Induction of MTMR3 Expression

Sun

et al. 2020

Preprint

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“…The traditional first-line chemotherapy with platinum-based drugs is still the main regimen for gastric cancer [20,21]. Although it is effective, its prominent disadvantages are severe side effects and drug resistance after repeated use [22,23]. However, the emerging peptide drugs have the advantages of small molecular weight, strong tissue permeability, low immunity, high affinity with the target and few side effects [24,25].…”

Section: Discussionmentioning

confidence: 99%

JP3, an antiangiogenic peptide, inhibits growth and metastasis of gastric cancer through TRIM25/SP1/MMP2 axis

Chen

Ren

Shu

et al. 2020

J Exp Clin Cancer Res

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Background: Gastric cancer (GC) is the most prevalent gastrointestinal tumor with an unfavorable clinical prognosis. GC patients are largely threatened owing to metastasis and drug resistance. Tumor angiogenesis plays an important role in the development of gastric cancer and is a challenge in the treatment of gastric cancer. Methods: Mouse xenograft models were used for screening of therapeutic peptides on GC growth and metastasis. Routine laboratory experimental methods including conditional cell culture, tube formation assay, qRT-PCR, Western blotting, immunohistochemistry (IHC), ubiquitination assay, and immunofluorescence (IF) were used in mechanism investigation; protein docking analysis and coimmunoprecipitation (Co-IP) were used for prediction and confirmation of interactions between JP3/SP1 and TRIM25/MEK1/2. Results: We identified an MMP2-targeted peptide JP3 that plays inhibiting roles in modulating growth and metastasis of GC in vivo and has no observable toxic side effects. JP3 reduced tumor microvessel density (MVD) in vivo and human umbilical vein endothelial cells (HUVECs) tube formation in vitro. Mechanistic studies revealed that JP3 reduces polyubiquitination-mediated degradation of TRIM25 by increasing the stability of TRIM25 through phosphorylating it at Ser12. TRIM25, as an E3 ubiquitin ligase, promoted the ubiquitin of SP1 at K610, further suppressed expression of MMP2 and inhibited angiogenesis in GC. Importantly, the inversely association between TRIM25 and SP1 protein level was further verified in human GC tissues. Decreased TRIM25 expression and increased SP1 expression in tumor tissues were positively correlated with poor prognosis of GC patients. Conclusions: MMP2-targeted peptide JP3 plays a therapeutic role in GC through anti-angiogenesis by modulating TRIM25/SP1/MMP2.

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“…MiR-421, a highly expressed miRNA in advanced gastric cancer patients, could also promote gastric cancer metastasis and DDP resistance through inhibiting E-cadherin and caspase-3 expression, in vivo and in vitro [91]. In addition, oncogenic miR-135b-5p, miR-135b, miR-17-5p, miR-193a-3p, miR-4295 and miR-3174 confer DDP resistance of gastric cancer cells through silencing Krüppel-like factor 4 (KLF4), mammalian ste20-like kinase 1 (MST1), p21, SRSF2, leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) and ARHGAP10, respectively [28,[92][93][94][95][96]. For oxaliplatin resistance, the oncogenic miR-27a has been found to enhance MDR properties by inducing MDR1/P-gp, lung resistance protein (LRP) and Bcl-2 expression in gastric cancer [97].…”

Section: Mirnas and Resistance To Platinum Drugsmentioning

confidence: 99%

Noncoding RNAs in gastric cancer: implications for drug resistance

et al. 2020

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Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.

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Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

Cited by 63 publications

References 57 publications

Circular RNA MCTP2 Inhibits Cisplatin Resistance in Gastric Cancer by miR-99a-5p-Mediated Induction of MTMR3 Expression

Circular RNA MCTP2 Inhibits Cisplatin Resistance in Gastric Cancer by miR-99a-5p-Mediated Induction of MTMR3 Expression

JP3, an antiangiogenic peptide, inhibits growth and metastasis of gastric cancer through TRIM25/SP1/MMP2 axis

Noncoding RNAs in gastric cancer: implications for drug resistance

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