Gastric cancer (GC) is the fifth most commonly diagnosed malignant disease and the third leading cause of cancer‑related deaths worldwide. Recently, numerous microRNAs (miRNAs) have been determined to contribute to GC initiation and progression, suggesting that miRNAs may be developed as effective diagnostic and prognostic molecular biomarkers and can be investigated as therapeutic targets for patients with this disease. Therefore, further investigation of the miRNAs involved in GC development represents an opportunity to improve the prognosis of GC patients. miRNA‑454 (miR‑454) is abnormally expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanism of miR‑454 in GC remain unclear and require further investigation. In the present study, we assessed miR‑454 expression in GC tissues and cell lines. We also explored the effects of miR‑454 on the biological behaviours of tumour cells and the underlying molecular mechanisms of miR‑454. The results revealed that miR‑454 was significantly downregulated in GC tissues and cell lines. Low miR‑454 expression was positively associated with lymph node metastasis, invasive depth and TNM stage. Additionally, upregulation of miR‑454 inhibited cell proliferation and invasion and induced the apoptosis of the GC cells. Subsequently, mitogen‑activated protein kinase 1 (MAPK1) was identified as a direct target of miR‑454. MAPK1 was upregulated in GC tissues and was found to be negatively correlated with the miR‑454 expression level. Downregulation of MAPK1 also suppressed GC cell proliferation and invasion and increased apoptosis, thereby resembling the suppressive effects of miR‑454 overexpression in GC. Moreover, upregulation of MAPK1 reversed the tumour‑suppressive effects of miR‑454 in GC. Collectively, our data demonstrated that miR‑454 may play tumour‑suppressing roles in GC through the regulation of MAPK1, suggesting that miR‑454 may be a novel biomarker and therapeutic target for patients with this disease.
Background: This study was aimed to determination the tumor inhibitory effect and explore the potential mechanisms of Lagopsis supine ethanol extract (Ls) on colorectal cancer. Methods: The cell growth inhibition experiment of Ls in colorectal cancer cell lines was determined by MTT method in the time course of 24, 48 and 72 h in four gradient drug concentrations. The protein expression levels of pSTAT3, pJAK2, STAT3, JAK2, Bcl-2 and caspase 3 were measured by Western blot method. The mRNA levels of the downstream genes of STAT3 were detected through semi-quantitative RT PCR. Sixty Balb/c-nude mice were xenograft with HCT116 colorectal cancer cells through subcutaneously. The xenografts were divided into five groups: model group, positive group (capecitabine 300 mg/kg) and three dosages of Ls treated groups (75, 150 and 300 mg/kg). Tumor size and tumor weight were calculated for evaluation the anti-tumor effects. H & E staining and immunohistochemical analysis were used to determine the histopathological changes and the levels of pSTAT3 and pJAK2 in the tumor tissues. Results: Ls exhibited a significant anti-proliferation effect in HCT116 and SW480 cells in vitro. The protein levels of pSTAT3, pJAK2 and Bcl-2, and the mRNA levels of Bcl-2 and Bak notably reduced with a dose-dependent manner. While the protein levels of caspase 3, and mRNA levels of Bax and caspase-3 remarkably increased in the gradient dosage of Ls in HCT116 cells. HCT116 in vivo xenografts experiment showed that the growth of the tumors significantly inhibited by Ls administration, which with no any significant body weight changes in each experiment group. The histopathology analysis displayed that Ls significantly reduced the inflammatory cells in tumor tissue. Furthermore, Ls also significantly down-regulate the protein levels of pSTAT3 and pJAK2 in the tumor tissues, compared with the model group. Conclusions: This work shows that Ls inhibited the cell proliferation of colorectal cancer in vitro and significantly reduced the tumor growth in HCT116 xenografts in vivo, which is probably related with the JAK/STAT signal pathway.
Following the publication of this paper, the authors have been unable to obtain consistent results after having repeated some of the flow cytometric assay experiments, undermining their confidence in the reported conclusions concerning the regulatory action of miR-454 on gastric cancer cell apoptosis. Consequently, owing to a lack of confidence in the presented data, the authors have requested that this paper be retracted from the journal.All authors agree with the retraction of this article, and apologize to the Editor and readership for the inconvenience caused.
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