LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are widely reported to be involved in the development of human diseases. HLA complex P5 (HCP5) deregulation is associated with various diseases. However, the function of HCP5 in diabetic nephropathy (DN) is unclear. METHODS: Human glomerular mesangial cells (HGMCs) were treated with high glucose (HG) to establish DN cell models. The expression of HCP5, miR-93-5p and high mobility group AT-hook 2 (HMGA2) mRNA was detected using quantitative polymerase chain reaction (QPCR). Cell proliferation and cell apoptosis were assessed using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of apoptosis- and fibrosis-related proteins and HMGA2 protein was quantified by western blot. The release of pro-inflammatory factor was checked using enzyme-linked immunosorbent assay (ELISA). The predicted relationship between miR-93-5p and HCP5 or HMGA2 was verified using dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay. RESULTS: The expression of HCP5 and HMGA2 was enhanced, while the expression of miR-93-5p was declined in DN serum samples and HG-treated HGMCs. HCP5 knockdown or miR-93-5p restoration ameliorated HG-induced HGMC proliferation, fibrosis and inflammation. MiR-93-5p was a target of HCP5, and miR-93-5p inhibition reversed the effects caused by HCP5 knockdown. Moreover, HMGA2 was a target of miR-93-5p, and HMGA2 overexpression abolished the effects of miR-93-5p restoration. HCP5 knockdown inhibited the AKT/mTOR signaling pathway. CONCLUSION: HCP5 was implicated in DN progression by modulating the miR-93-5p/HMGA2 axis, which provided new insights into the understanding of DN pathogenesis.

Circulating cell-free high mobility group AT-hook 2 mRNA as a detection marker in the serum of colorectal cancer patients.

BACKGROUND: Detection of circulating cell-free mRNA serves as noninvasive tools for cancer diagnosis. As an oncofetal protein, HMGA2 (high mobility group AT-hook 2) is upregulated in colorectal cancer (CRC) tissues. However, it is not clear whether the increased levels of circulating cell-free HMGA2 mRNA functions as potential biomarkers for improved diagnosis of CRC. METHODS: To assess its clinical significance in diagnosis and prediction, we evaluated serum levels of circulating HMGA2 mRNA in CRC patients and in healthy controls. In this study, 83 CRC patients and 11 normal controls were enrolled in this study. We used real-time quantitative reverse transcription-PCR to evaluate the plasma mRNA levels of HMGA2 and analyze the correlation between their expression and clinicopathologic characteristics. RESULTS: We found that the levels of HMGA2 mRNA were significantly higher in CRC patients compared with healthy volunteers. The patients with right-sided CRC, colon cancer, positive nerve infiltration, positive vascular invasion, negative microsatellite instability (MSI), and increasing in serum carbohydrate antigen (CA) 199 had higher levels of plasma HMGA2 mRNA. A strong positive correlation between circulating cell-free HMGA2 mRNA and CA199 level in serum was found in our study. Furthermore, statistical analysis revealed that levels of HMGA2 mRNA in plasma and in tumors were strictly correlated. CONCLUSIONS: Collectively, our data suggested that cell-free HMGA2 mRNA in plasma might function as a novel diagnostic marker for CRC.

Circulating high mobility group AT-hook 2 and pleomorphic adenoma gene 1 in blood of patients with oral squamous cell carcinoma.

BACKGROUND: High mobility group AT-hook 2 (HMGA2) and pleomorphic adenoma gene 1(PLAG1) have been demonstrated to be elevated in many malignant tumors. However, the aim of this study was to evaluate HMGA2 and PLAG1 levels in blood as a non-invasive biomarker for oral squamous cell carcinoma (OSCC) diagnosis. METHODS: qRT-PCR was performed to measure circulating HMGA2 and PLAG1 levels in OSCC patients (n=43) and matched cancer-free blood control group (n=21). Clinical data of all patients were recorded. RESULTS: Circulating HMGA2 and PLAG1 in the 43 OSCC patients was significantly higher than in control group (P<.001, P=.038, respectively). Furthermore, HMGA2 expression in OSCC patients with poor-moderate differentiation was increased compared with well-differentiated group. However, no significant differences in PLAG1 expression were detected when differentiation was considered. In addition, the receiver operating characteristic (ROC) curve analysis for circulating HMGA2 revealed an area under the ROC curve of 0.876 (95% confidence interval, 0.793-0.959; P<.001) with 65.1% sensitivity and 100% specificity in discriminating OSCC from controls at a cutoff value of 14.380, demonstrating significant diagnostic value for OSCC. CONCLUSION: Circulating HMGA2 levels are increased in OSCC patients and may potentially serve as a significant index to evaluate OSCC diagnosis.

Clinicopathologic significance of HMGA2 expression's correlation with prognosis of esophageal squamous cell carcinoma after Ivor Lewis esophagectomy.

UNLABELLED: BACKGROUNDː The main reason for the commonly poor prognosis of esophageal squamous cell carcinoma (ESCC) after surgery is the high recurrence rate. For patients at high risk of recurrence, it may be of value to seek indicators of recurrence, which would be useful for further treatment. High-mobility group A2 (HMGA2) is a small non-histone chromosomal protein, highly expressed in many epithelial tissue malignant tumors and closely correlated with the occurrence, development and prognosis of tumor. Its aberrant expression in various cancers was detected, while its expression and significance in ESCC is still unclear. METHODSː We enrolled 127 patients with ESCC who had undergone Ivor-Lewis esophagectomy. The expression profile of HMGA2 was examined by immunohistochemistry. RESULTS: The result showed that the high expression of HMGA2 correlated with a higher T stage (P=0.007), lower differentiation degree (P=0.008), lymph node metastasis (P<0.01), recurrence status (P=0.005) and TNM stage (P=0.006). The Cox regression analysis showed that the TNM stage (P=0.006), differentiation degree (P=0.003) and high HMGA2 expression (P=0.048) were independent risk factors of survival. CONCLUSIONSː Our data indicated that HMGA2 expression level associates with key clinicopathological features and could be an effective biomarker to predict the prognosis of ESCC.