Background
Increasing studies have shown that long noncoding RNAs (lncRNAs) are pivotal regulators participating in carcinogenic progression and tumor metastasis in colorectal cancer (CRC). Although lncRNA long intergenic noncoding RNA 460 (LINC00460) has been reported in CRC, the role and molecular mechanism of LINC00460 in CRC progression still requires exploration.
Methods
The expression levels of LINC00460 were analyzed by using a tissue microarray containing 498 CRC tissues and their corresponding non-tumor adjacent tissues. The correlations between the LINC00460 expression level and clinicopathological features were evaluated. The functional characterization of the role and molecular mechanism of LINC00460 in CRC was investigated through a series of in vitro and in vivo experiments.
Results
LINC00460 expression was increased in human CRC, and high LINC00460 expression was correlated with poor five-year overall survival and disease-free survival. LINC00460 overexpression sufficiently induced the epithelial–mesenchymal transition and promoted tumor cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. In addition, LINC00460 enhanced the protein expression of high-mobility group AT-hook 1 (HMGA1) by directly interacting with IGF2BP2 and DHX9 to bind the 3′ untranslated region (UTR) of HMGA1 mRNA and increased the stability of HMGA1 mRNA. In addition, the N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC. Finally, it suggested that HMGA1 was essential for LINC00460-induced cell proliferation, migration, and invasion.
Conclusions
LINC00460 may be a novel oncogene of CRC through interacting with IGF2BP2 and DHX9 and bind to the m6A modified HMGA1 mRNA to enhance the HMGA1 mRNA stability. LINC00460 can serve as a promising predictive biomarker for the diagnosis and prognosis among patients with CRC.
Objective Chromium-containing traditional Chinese medicine Tianmai Xiaoke tablet (TMXKT) is approved for treating newly diagnosed type 2 diabetes mellitus (T2DM) in China. This review aimed to compile the evidence from randomized clinical trials (RCTs) and quantify the effects of TMXKT on newly diagnosed T2DM. MethodsSeven online databases were investigated up to March 20, 2017. The meta-analysis included RCTs investigating the treatment of newly diagnosed T2DM, in which TMXKT combined with conventional therapy was compared with placebo or conventional therapy. The risk of bias was evaluated using the Cochrane Collaboration tool. The estimated mean difference (MD) and the standardized mean difference were within 95% confidence intervals (CI) with respect to the interstudy heterogeneity. The outcomes were measured using fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), glycosylated hemoglobin A1c (HbA1c), and body mass index (BMI) levels. ResultsTMXKT combined with conventional therapy lowered FBG level (MD = −0.68, 95% CI −0.90 to −0.45, P < 0.00001), 2hPG (MD = −1.33, 95% CI −1.86 to −0.79, P < 0.00001), HbA1c (MD = −0.46, 95% CI −0.57 to −0.36, P < 0.00001), and BMI (MD = −0.77, 95% CI −1.12 to −0.41, P < 0.00001). ConclusionsTMXKT combined with conventional therapy is beneficial for patients with newly diagnosed T2DM. However, the effectiveness and safety of TMXKT are uncertain because of the limited number of trials and low methodological quality. Therefore, practitioners should be cautious when applying TMXKT in daily practice. Also, well-designed clinical trials are needed in the future.
Histone deacetylase 6 (HDAC6), a specific histone deacetylase family member, serves an essential role in the regulation of gene expression, cell cycle progression, autophagy and apoptosis. There are numerous reports on the function of HDAC6 in cancer. However, the specific function of HDAC6 in hepatocellular carcinoma (HCC) has yet to be revealed. In the present study, the expression of HDAC6 was revealed to be downregulated in human HCC cell lines and tissues. The aberrant activation of the canonical Wnt/β-catenin signaling pathway was revealed to be involved in hepatocarcinogenesis and metastasis. It was additionally revealed that the overexpression of HDAC6 decreased the expression of β-catenin protein levels which attenuated the canonical Wnt/β-catenin signaling pathway and suppressed the proliferation of HCC cells. In addition, the upregulation of HDAC6 inhibited the epithelial-to-mesenchymal transition in HCC by increasing the E-cadherin protein levels and decreasing the N-cadherin, vimentin and matrix metalloproteinase-9 protein levels. Furthermore, HDAC6 also exerted an effect on the cell cycle arrest and the induction of apoptosis. These results demonstrated that HDAC6 functioned as a tumor suppressor in HCC by attenuating the activity of the canonical Wnt/β-catenin signaling pathway. Therefore, HDAC6 may serve as a potential therapeutic target for the treatment of HCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.