Our results demonstrated that miR-92a induced EMT and regulated cell growth, migration and invasion in the SW480 cells, at least partially, via suppression of PTEN expression. MiR-92a may serve as a novel therapeutic target in colorectal cancer.

BackgroundMicroRNAs(miRNAs) are small non-coding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-378 has been found in some types of cancer. However, effects and potential mechanisms of miR-378 in colorectal cancer (CRC) have not been explored.MethodsQuantitative RT-PCR was performed to evaluate miR-378 levels in CRC cell lines and 84 pairs of CRC cancer and normal adjacent mucosa. Kaplan–Meier and Cox proportional regression analyses were utilized to determine the association of miR-378 expression with survival of patients. MTT and invasion assays were used to determine the role of miR-378 in regulation of CRC cancer cell growth and invasion, respectively. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Luciferase assay was performed to assess miR-378 binding to vimentin gene.ResultsIn this study, we confirmed that miR-378 significantly down-regulated in CRC cancer tissues and cell lines. Moreover, patients with low miR-378 expression had significantly poorer overall survival, and miR-378 expression was an independent prognostic factor in CRC. Over-expression of miR-378 inhibited SW620 cell growth and invasion, and resulted in down-regulation of vimentin expression. However, miR-378 knock-down promoted these processes and enhanced the expression of vimentin. In addition, we further identified vimentin as the functional downstream target of miR-378 by directly targeting the 3′-UTR of vimentin.ConclusionsIn conclusion, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion. Our present results implicate the potential effects of miR-378 on prognosis and treatment of CRC cancer.

BackgroundGrowing evidence suggests that microRNAs (miRNAs) play an important role in tumor development, progression and metastasis. Aberrant miR-106b expression has been reported in several cancers. However, the role and underlying mechanism of miR-106 in colorectal cancer (CRC) have not been addressed.MethodsQuantitative RT-PCR(qRT-PCR) was performed to evaluate miR-106b levels in CRC cell lines and patient specimens. Cell proliferation was detected using MTT assay, and cell migration and invasion ability were evaluated by wound healing assay and transwell assay. The target gene of miR-106b was determined by qRT-PCR, western blot and luciferase assays.ResultsmiR-106b was significantly up-regulated in metastatic CRC tissues and cell lines, and high miR-106b expression was associated with lymph node metastasis and advanced clinical stage. In addition, miR-106b overexpression enhances, whereas miR-106b depletion reduces CRC cell migration and invasion. Moreover, we identify DLC1 as a direct target of miR-106b, reveal its expression to be inversely correlated with miR-106b in CRC samples and show that its re-introduction reverses miR-106b-induced CRC cell migration and invasion. Furthermore, survival analyses showed the patients with high mi-106b/low DLC1 had shorter overall survival (OS) and disease-free survival (DFS) rates, and confirmed miR-106b may be an independent prognostic factor for OS and DFS in CRC patients.ConclusionsOur findings indicate that miR-106b promotes CRC cell migration and invasion by targeting DLC1. This miRNA may serve as a potential prognostic biomarker and therapeutic target for CRC.

Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers. MicroRNAs (miRNAs) have been proved to be unusually expressed in CRC progression and thus alter multiple pathological processes in CRC cells. However, the specific roles and mechanisms of miR-22 in CRC have not been clearly reported. MicroRNA-22 (miR-22) and MYC-associated factor X (MAX) expressions were determined by RT-qPCR in CRC tissues and cells. The targeted regulatory effects of miR-22 and MAX were confirmed by luciferase reporter and coimmunoprecipitation assays. Also, gain- and loss-of-function and rescue experiments were used to elucidate the function and mechanism of miR-22 and MAX in CRC cells and the mouse xenograft model. We discovered that miR-22 was hypermethylated and downregulated, while MAX was upregulated in CRC. miR-22 markedly inhibited migration, invasion, glycolysis, and cancer stem cell transcription factors in CRC cells. In addition, it was found that miR-22 can directly target MAX. Additional functional experiments confirmed that MAX overexpression can rescue the effects of miR-22 on the behavior of CRC cells. This study suggested that miR-22, as a cancer suppressor, participates in CRC progression by targeting MAX, which might provide basic information for therapeutic targets for CRC.

Background: The morbidity and mortality of rectal adenocarcinoma (READ) is increasing, which is considered as an aggressive type of colorectal malignancy. A great deal of evidence has suggested the significant association between the progression of READ and the immunophenotype of tumor cells (i.e. the expression of intracellular immune-related genes).Methods: Samples retrieved from the TCGA and ImmPort database were investigated to identify immune-related genes specifically impacting the prognosis of READ patients. Several typical ones were then selected to construct the prognostic prediction model of READ patients through Lasso algorithm. The training and test cohorts were incorporated into the model, respectively. We stratified READ patients to evaluate the accuracy, efficiency and stability of the model in the prediction and classification of patient prognosis according to the value of median RiskScore (Risk-H and Risk-L). GO and KEGG signaling pathway enrichment analysis were conducted among the nine selected immunerelated genes. Results: A total of 57 immune-related displaying marked correlated with patient prognosis were identified and nine most typical genes could be majorly enriched into several pathways with close correlation with READ and the corresponding immune response. the distribution of nine immunerelated genes were examined in the samples from both Risk-H and -L groups. Finally, the connection of the RiskScore value with the clinical characteristics of sample and the related signaling pathways were investigated. Conclusions: The prognostic prediction model of RiskScore constructed based on the expression profiling of the nine immune-associated genes exhibited high prediction accuracy and stability to identify the relevant immune features. This model could contribute to the guidance for clinicians in diagnosing and predicting the prognosis for various immunophenotypes. Meanwhile, it also can offer various therapeutic targets for precise treatment of READ in clinical practice according to the identified immune molecules specific to different subtypes. 14 READ: rectal adenocarcinoma; TCGA: the cancer genome atlas; ROC: Receiver Operating Characteristic Curves; HGNC: hugo gene nomenclature committee; KEGG: Kyoto Encyclopedia of Genes and Genomes.