Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. The role of the differentially expressed lncRNAs in 5-Fluorouracil chemoresistance has not fully explained. Here, we observed lncRNA H19 was associated with the 5-Fu resistance in CRC. Quantitative analysis indicated that H19 was significantly increased in recurrent CRC patient samples. Kaplan–Meier survival analysis indicated that high H19 expression in CRC tissues was significantly associated with poor recurrent free survival. Our functional studies demonstrated that H19 promoted colorectal cells 5-Fu resistance. Mechanistically, H19 triggered autophagy via SIRT1 to induce cancer chemoresistance. Furthermore, bioinformatics analysis showed that miR-194–5p could directly bind to H19, suggesting H19 might work as a ceRNA to sponge miR-194–5p, which was confirmed by Dual-luciferase reporter assay and Immunoprecipitation assay. Extensively, our study also showed that SIRT1 is the novel direct target of miR-194–5p in CRC cells. Taken together, our study suggests that H19 mediates 5-Fu resistance in CRC via SIRT1 mediated autophagy. Our finding provides a novel mechanistic role of H19 in CRC chemoresistance, suggesting that H19 may function as a marker for prediction of chemotherapeutic response to 5-Fu.

Approximately 20% of HER2 positive breast cancer develops disease recurrence after adjuvant trastuzumab treatment. This study aimed to develop a molecular prognostic model that can reliably stratify patients by risk of developing disease recurrence. Using miRNA microarrays, nine miRNAs that differentially expressed between the recurrent and non-recurrent patients were identified. Then, we validated the expression of these miRNAs using qRT-PCR in training set (n = 101), and generated a 2-miRNA (miR-4734 and miR-150-5p) based prognostic signature. The prognostic accuracy of this classifier was further confirmed in an internal testing set (n = 57), and an external independent testing set (n = 53). Besides, by comparing the ROC curves, we found the incorporation of this miRNA based classifier into TNM stage could improve the prognostic performance of TNM system. The results indicated the 2-miRNA based signature was a reliable prognostic biomarker for patients with HER2 positive breast cancer.

d MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment. Colorectal cancer (CRC) is the third most common cancer in males and females, with an estimated 142,820 new cases and 50,830 deaths in the United States in 2013. The overall CRC incidence is 5% in the general population, and the 5-year survival rate ranges from 40% to 60% (1). Despite the improvement of currently available treatment strategies, including surgical resection, radiotherapy, and chemotherapy, the survival rate of patients with CRC has changed little over the past 10 years. Almost 50% of CRC patients will die of the disease, mainly due to metastasis to the liver. Thus, it is imperative to achieve earlier diagnosis and better tailoring of treatments to improve CRC outcomes.MicroRNAs (miRNAs) are a family of endogenous small noncoding RNAs that regulate gene expression via the sequence-specific base pairing on the 3= untranslated regions (3= UTRs) of target mRNAs, resulting in mRNA cleavage or translation inhibition (2). More than 30% of the protein-coding genes are controlled by miRNAs, as indicated by bioinformatics predictions. miRNAs are involved in a plethora of biological processes, such as proliferation, migration, invasion, and apoptosis (3, 4). In recent years, miRNAs have been recognized as critical regulators in development and progression of cancer, including CRC (5-8).miRNA 30a (miR-30a) is a member of the miR-30 family, which consists of six distinct mature miRNA sequences: miR-30a/ miR-30c-2, miR-30d/miR-30b, and miR-30e/miR-30c-1 (9). There is considerable evidence suggesting that the dysregulation of miR-30a is correlated with several types of malignant tumors, including breast cancer, lung cancer, thyroid cancer, gastric cancer, and leuke...

Apolipoprotein E (ApoE) plays a key role in tumorigenesis and progression, such as cell proliferation, angiogenesis and metastasis. ApoE overexpression was associated with aggressive biological behaviors and poor prognosis in a variety of tumor according to previous studies. This study aimed to assess the prognostic value and explore the potential relationship with tumor progression in colorectal cancer (CRC). We collected the expression profiling microarray data from the Gene Expression Omnibus (GEO), investigated the ApoE expression pattern between the primary CRC and liver metastasis of CRC, and then explored the gene with prognostic significance based on the TCGA database. ApoE high expression was associated with poor overall survival (OS, p = 0.015) and progression-free survival (PFS, p = 0.004) based on the public databases. Next, ApoE expression was evaluated in two CRC cohorts by immunohistochemistry, of whom 306 cases were stage II and 201 cases were metastatic liver CRC. In the cohort of the liver metastasis, the ApoE expression was increasing in normal mucosa tissue, primary colorectal cancer (PC), and colorectal liver metastases (CLM) in order. Meanwhile, the level of ApoE expression in stage II tumor sample which had no progression evidence in 5 years was lower than that in PC of synchronous liver metastases. The high ApoE expression in PC was an independent risk factor in both stage II (HR = 2.023, [95% CI 1.297–3.154], p = 0.002; HR = 1.883, [95% CI 1.295-2.737], p = 0.001; OS and PFS respectively) and simultaneous liver metastasis (HR = 1.559, [95% CI 1.096–2.216], p = 0.013; HR = 1.541, [95% CI 1.129–2.104], p = 0.006; OS and PFS respectively). However, the overexpression of ApoE could not predict the benefit from the chemotherapy in stage II. The study revealed that the relevance of the ApoE overexpression in CRC progression, conferring a poor prognosis in CRC patients especially for stage II and simultaneous liver metastasis. These finding may improve the prognostic stratification of patients for clinical strategy selection and promote CRC clinic outcomes.