Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression

Tse, Janson W.T.; Pierce, Thomas P.; Carli, Annalisa L E; Alorro, Mariah; Thiem, Stefan; Marcusson, Eric G.; Ernst, Matthias; Büchert, Michael

doi:10.3390/cancers14020264

Cited by 16 publications

(10 citation statements)

References 72 publications

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“…This microRNA has an oncogenic role and by turning off a series of important genes in the cell, it leads the cell to become cancerous. There are traces of this micro RNA in various cancers (16). In this study, which was performed on 40 patients with cardia gastric cancer and 40 healthy individuals were selected as a control group, we found a direct relationship between increased expression of miR-21 and tumor staging.…”

Section: Resultsmentioning

confidence: 64%

Evaluation of increased microRNA-21 in the serum of patients with cardia cancer

He¹,

Zhou²

2022

Cell Mol Biol (Noisy-le-grand)

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MicroRNAs are a new group of regulatory RNAs that are about 22 nucleotides long. MicroRNAs are also involved in many human cancers and can actually act as oncogenes and suppressors. In this study, the relationship between miR-21 levels in the serum of sick and healthy individuals and the relationship between high concentrations of this microRNA and tumor staging and cancer progression was performed for the first time in Iran on gastric cardia cancer. This study was performed on 40 patients with gastric cardia cancer and 40 patients who were selected as a control group. The control group was selected from those who presented due to gastrointestinal disorders but were diagnosed as healthy or non-cancerous. Their serum miR-21 was measured using the Real-Time PCR technique. The relationship between the concentration of this microRNA in serum with tumor staging and cancer progression was evaluated. Findings showed that increasing the concentration of miR-21 in serum samples, serum miR-21 in patients was about 3.5 times that of controls (P <0.0001), and serum miR-21 in patients was significantly related to staging tumor showed (P = 0.01), indicating a significant and direct relationship between miR-21 and tumor growth, which indicates the importance of this microRNA in the progression of gastric cancer. Given the role of miR-21 in the progression of gastric cardia cancer and its association with clinic-pathological factors, it can be introduced as a new diagnostic marker. It can also be used as a non-invasive method in the early diagnosis of gastric cancer patients. In this study, miR-21 has an oncogenic role that can be measured in patients' serum to assess the progression of gastric cancer.

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Section: Resultsmentioning

confidence: 64%

Evaluation of increased microRNA-21 in the serum of patients with cardia cancer

He¹,

Zhou²

2022

Cell Mol Biol (Noisy-le-grand)

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“…Inhibition of miR21 expression has been shown to suppress tumor growth and induce apoptosis in gastric cancer cells. [59][60][61][62] Recent studies show that miR 135b plays a crucial role in the progression of gastric cancer and several factors have been identified to contribute to the overexpression of miR 135b, including Helicobacter pylori. 15,[63][64] One study investigated the effect of miR-135b on gastric cancer growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

A case series and a systematic review of the literature on upregulated miRs in gastric cancer: a story still to be told.

Lorenzon

Belia

French³

et al. 2023

Preprint

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Background: Recent literature documented the expression of miRs in gastric cancer (GC), however their clinical utility is still unclear. Methods and Results: 117 resected GCs were evaluated for miR21, miR135b, miR196a, miR196b relative expression (RE). The performance of miRs’ to differentiate cancer vs normal mucosa was tested using ROC curves. Univariable and multivariable analyses were conducted to correlate miRs RE with pathological features and survivals. Although all the 4 miRs were upregulated, ROC curves documented that this was not-significant in differentiating GC (p ns). miR135b significantly correlated with Lauren’s intestinal type and more advanced pT stages (p 0.017, and p 0.025), whereas miR196a and miR196b were more expressed in advanced pStages (p 0.016, and p 0.038). miR196b was also more expressed in nodal positive patients comparing N0 (p 0.035). Survival curves were non-significant for miRs RE, while pStages could significantly differentiate oncological outcomes (p<0.0001). On Cox analyses, pStages independently correlated with OS (HR 4.9, 95%CI 2.041-12.104), whereas increased age correlated with a worse DFS (HR 6.0, 95%CI 2.596-13.947), and lymph-node ratio with DSS (HR 14.4, 95%CI 4.213-49.373). Literature was reviewed a using PRISMA method focusing on miRs and response to therapy and the detection of peritoneal metastases: out of 116 manuscripts retrieved, just 41 were pertinent with the outcomes of interest, and 14.6% were from Western countries. miR21, miR135b and miR204 were reported to correlate with response to therapy. Conclusions: miR21, miR135b, miR196a and miR196b were documented up-regulated in GC, but their clinical utility is still to be fully investigated.

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“…Many studies have shown that constitutive STAT3 is activated in a variety of human tumors ( Grandis et al, 2000 ). Evidence suggests that abnormal STAT3 signaling promotes the occurrence and development of human cancers by inhibiting apoptosis, inducing cell proliferation, angiogenesis, invasion, and metastasis ( Melinda et al, 2000 ; Leong et al, 2003 ; Bollrath et al, 2009 ; Zhu et al, 2019 ; Chen et al, 2020 ), as well as inducing inflammation and immunosuppression ( Leaman et al, 1996 ; Mohan et al, 2022 ; Tse et al, 2022 ). In OSCC studies, STAT3 is the most common signal transducer and activator of transcription.…”

Section: Discussionmentioning

confidence: 99%

CircPUM1 Knockdown Confers Radiosensitivity in Oral Squamous Cell Carcinoma by Regulating the miR-580/STAT3 Pathway

et al. 2022

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Background: CircPUM1 acts as an oncogene in a variety of tumors, and there is no related research on oral squamous cell carcinoma. This study aimed to evaluate the clinical significance of CircPUM1 in oral squamous cell carcinoma radiotherapy.Methods: Radio-resistant cell lines were established by increasing the X-ray dose. Analysis of CircPUM1 expression in oral squamous cell carcinoma was carried out using bioinformatics tools. Cell proliferation was analyzed with CCK-8 and colony formation. Protein and gene expressions were detected by Western blotting and qPCR. RNA interference inhibits endogenous gene expression. A luciferase reporter system and immunoprecipitation were used to validate the target of CircPUM1.Result: CircPUM1 was highly expressed in OSCC. The higher the expression level of CircPUM1 in OSCC, the worse the clinical features and prognosis. Knockdown of CircPUM1 enhances the sensitivity of OSCC cells to X-rays, and expression of exogenous CircPUM1 makes OSCC cells acquire radiation resistance. The absence of CircPUM1 blocked the cells in the G0/G1 phase and triggered apoptosis. The prediction of mir-580-binding site, luciferase reporter system, and immunoprecipitation confirmed that mir-580 is the binding site of CircPUM1. In addition, STAT3 was predicted and confirmed as the binding site of mir-580. Overexpression of STAT3 partially attenuated the radiosensitivity of OSCC cells to knockdown of CircPUM1.Conclusion: CircPUM1 has the oncogene expression profile in oral squamous cell carcinoma; patients with high expression of CircPUM1 have less benefit from radiotherapy and need more frequent follow-up. In addition, CircPUM1 may be a potential therapeutic target for oral squamous cell carcinoma. The CircPUM1/mir-580/STAT3 axis has a certain effect on the radiosensitivity of OSCC. These results suggest that patients with low expression of CircPUM1 may gain more benefits.

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Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression

Cited by 16 publications

References 72 publications

Evaluation of increased microRNA-21 in the serum of patients with cardia cancer

Evaluation of increased microRNA-21 in the serum of patients with cardia cancer

A case series and a systematic review of the literature on upregulated miRs in gastric cancer: a story still to be told.

CircPUM1 Knockdown Confers Radiosensitivity in Oral Squamous Cell Carcinoma by Regulating the miR-580/STAT3 Pathway

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