miR-218 suppresses tumor growth and enhances the chemosensitivity of esophageal squamous cell carcinoma to cisplatin

Tian, Heshen; Hou, Lei; Xiong, Ye; Huang, Junxiang; She, Ying-Jun; Bi, Xiaobao; Song, Xingrong

doi:10.3892/or.2014.3657

Cited by 28 publications

(22 citation statements)

References 43 publications

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“…These miRNAs are associated with different etiologies, metastasis, the propensity for recurrence and prognosis as a molecular signature in human types of cancer (10,11). Recent findings have showed that miRNAs are important in the drug resistance of different tumors (12)(13)(14). Given the close relationship between miRNAs and the biological progression of various types of cancer, miRNAs are considered potential novel targets for the therapy of various types of cancer (15).…”

Section: Introductionmentioning

confidence: 99%

miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN

et al. 2015

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Abstract. acts as an oncomiR and is involved in tumor development, progression and metastasis, and confers resistance to chemotherapeutic drugs by targeting a number of molecules in several human cancers. However, the function and underlying molecular mechanism of miR-494 in hepatocellular carcinoma (HCC) has not been totally elucidated. In the present study, we determined the role played by miR-494 in HCC tissues and HCC cell lines using quantitative RT-PCR (RT-qPCR). The results showed that, miR-494 was significantly upregulated in HCC tissues and HCC cell lines. Additionally, a high miR-494 expression positively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Luciferase reporter assays confirmed that miR-494 binds to the 3'-untranslated region (3'-UTR) of the phosphatase and tensin homolog (PTEN) mRNA and represses its translation. Functional analyses indicated that the upregulation of miR-494 promoted cell viability, migration and invasion, decreased cell apoptosis and cell cycle arrest at G1 stage, and conferred sorafenib resistance to HCC cell lines. Underexpression of PTEN by siRNA significantly attenuated the inhibitory effects of anti-miR-494 on the proliferation, migration and invasion of liver cancer cells. Mechanistic investigations revealed that miR-494 suppressed the expression of PTEN but increased the expression of PI3K and p-Akt, which contribute to the promotion of proliferation, migration and invasion, and increased sorafenib resistance to HCC cell lines. These findings suggested that miR-494 is a potential candidate for HCC therapeutics.

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Section: Introductionmentioning

confidence: 99%

miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN

et al. 2015

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“…Reports also showed that miR-218 might act as tumor suppressor in a variety of human cancer types [12,15,16]. In addition, increased expression of miR-218 can enhance the chemosensitivity to cisplatin [17,18]. These results indicated that miR-218 may have a correlation with the resistance during lung cancer chemotherapy.…”

Section: Introductionmentioning

confidence: 71%

“…Extensive studies have indicated that tumor-targeting therapies using miRNAs are becoming a novel diagnostic and therapeutic tool [21]. A number of studies have indicated that miR-218 is involved in the chemosensitivity to cisplatin process in certain tumors and that upregulation of miR-218 may partially enhance cell death [17,18]. Consistently, in our present study, miR-218 was noteworthy downregulated in the A549/DDP cisplatin-resistant lung cancer cell lines compared with that in non-resistant A549 cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2

Xie

et al. 2015

Tumor Biol.

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Downregulation of microRNA-218 (miR-218) is found in various human cancers, including non-small cell lung cancer (NSCLC). However, the involvement of chemosensitivity to cisplatin (DDP) and the underlying molecular mechanism remain unclear. In this study, we investigate whether miR-218 mediates NSCLC cell functions associated with chemoresistance. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-218 expression in NSCLC cell lines A549/DDP and/or A549. The cell activity was measured by MTT assay. Cell cycle and cell apoptosis were detected by flow cytometry. Luciferase reporter assays and Western blots were used to validate runt-related transcription factor 2 (RUNX2) as a direct target gene of miR-218. miR-218 was significantly reduced in A549/DDP cells compared with parent A549 cells. Upregulation of miR-218 altered cell cycle-induced cell apoptosis and enhanced the sensitivity of A549/DDP cells to cisplatin. Mechanistically, RUNX2 was identified as a direct and functional target of miR-218, and RUNX2 executed the former on lung cancer chemoresistance. Our present study demonstrated for the first time that downregulation of miR-218 may contribute to the chemoresistance of NSCLC cells to cisplatin, which leads to upregulation of RUNX2. Uncovering the mechanism represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment.

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“…Aberrant expression of miRNAs is associated with tumor development through regulation of their respective target genes. For example, miR-218 was reported to suppress the growth of esophageal squamous cell carcinoma by regulating the PI3K/AKT/mTOR pathway (14). miR-17 and miR-106b are frequently downregulated in the serum of gastric cancer patients, which may therefore be utilized as tumor markers for the early diagnosis of gastric cancer (15).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-101 sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis via targeting Mcl-1

Tian

Chen

et al. 2015

Molecular Medicine Reports

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Abstract. MicroRNAs (miRNAs/miRs) are important regulators of multiple cellular processes, and their dysregulation is a common event in tumorigenesis, including the development of hepatocellular carcinoma (HCC). Studies have shown that certain miRNAs are associated with resistance to chemotherapy or drug sensitization; however, the underlying mechanisms have largely remained elusive. Multiple drug resistance is a major barrier for the treatment of advanced HCC. In the present study, miR-101 was observed to be downregulated in a panel of HCC cell lines, suggesting that it has a tumor suppressor role.

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miR-218 suppresses tumor growth and enhances the chemosensitivity of esophageal squamous cell carcinoma to cisplatin

Cited by 28 publications

References 43 publications

miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN

miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN

MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2

MicroRNA-101 sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis via targeting Mcl-1

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