Downregulation of MicroRNA-147 Inhibits Cell Proliferation and Increases the Chemosensitivity of Gastric Cancer Cells to 5-Fluorouracil by Directly Targeting PTEN

Shen, Jianjun; Niu, Weina; Ma, Jingfei; Zhang, Hongyan

doi:10.3727/096504017x15061902533715

Cited by 42 publications

(35 citation statements)

References 49 publications

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“…28,29 Shen et al found that knockdown of miR-147 enhanced the sensitivity of gastric cancer cells to 5-Fu by targeting PTEN and regulating the AKT signaling. 30 Meanwhile, miR-21 could enhance drug resistance to 5-Fu in PANC-1 cells by downregulation of PTEN. 31 In this study, we found that the downregulation of miR-486-5p markedly enhanced the anti-tumor effects of 5-Fu in PANC-1 cells via upregulating the expression of PTEN and suppressing the activation of AKT/ERK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

Wang

Liu

Sun

et al. 2020

OTT

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These authors contributed equally to this work Background: 5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Methods: Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay. Results: In this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the proapoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model. Conclusion: We found that the downregulation of miR-486-5p could enhance the antitumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

Wang

Liu

Sun

et al. 2020

OTT

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“…17 Furthermore, miRNA-147 can inhibit cell proliferation and increase the chemosensitivity of GC to 5-FU by targeting PTEN. 18 It seems that the status of PTEN and FAK expression may be helpful for evaluating the response to target therapy and chemotherapy. Our study demonstrated distinguishable patient prognoses according to the PTEN/FAK expression, which may provide useful information and have clinical impact on GC treatment.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Implication of PTEN and FAK Expression in Gastric Cancer Patients

Lai

Huang

Chen

et al. 2019

International Surgery

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Objective: The tumor suppressor gene phosphatase and tensin homolog (PTEN) was reported to inhibit the growth and invasion of gastric cancer (GC) via the downregulation of focal adhesion kinase (FAK). To date, the clinical implication of PTEN and FAK expression in GC has not been well addressed.Methods: A total of 200 GC patients receiving curative surgery were enrolled. The clinicopathologic features according to the expression of PTEN and FAK protein using immunohistochemical staining were compared among patients.Results: Patients with high PTEN expression were more likely to have smaller tumor size, more well-and moderately differentiated tumors, a more superficial gross appearance, less scirrhous stromal reactions, more likely to have high FAK expression, and have less advanced pathologic tumor (T) category, node (N) category, and tumor, node, metastasis (TNM) stage and more distant metastases than patients with low PTEN expression. Multivariate analysis showed that PTEN/FAK expression status is an independent prognostic factor affecting overall survival (OS) and disease-free survival (DFS). Patients with PTEN(high)/FAK(low) had better OS and DFS, followed by those with PTEN(high)/

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“…It has been found that EB virus miRNA miR-BART20-5p significantly increased 5-FU resistance of AGS1 gastric cancer cells by inhibiting BAD expression [56]. Similarly, miR-193-3p and miR-147 could promote 5-FU resistance of gastric cancer cells via directly suppressing their target gene PTEN [127,128]. Oncogenic miR-17 has been found to reduce 5-FU sensitivity of gastric cancer cells through silencing expression of DEDD [129].…”

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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Downregulation of MicroRNA-147 Inhibits Cell Proliferation and Increases the Chemosensitivity of Gastric Cancer Cells to 5-Fluorouracil by Directly Targeting PTEN

Cited by 42 publications

References 49 publications

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

The Clinical Implication of PTEN and FAK Expression in Gastric Cancer Patients

Noncoding RNAs in gastric cancer: implications for drug resistance

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