Mingxia Yu

Increased expression of long-noncoding RNA ZFAS1 is associated with epithelial-mesenchymal transition of gastric cancer.

LncRNAs play critical roles in gastric cancer (GC). In this study, the expression of fourteen cancer related lncRNAs were investigated in paired tissues of 66 patients with GC, Realtime RT-PCR revealed that ZFAS1 was significantly upregulated. We then examined the expression of ZFAS1 in plasmas derived from 77 GC patients before- and post-operations and 60 healthy individuals, and found that circulating ZFAS1 was also upregulated in GC patients and operation can reduce its presence in plasma. To investigate the potential mechanisms, we compared the expression of ZFAS1 in multiple gastric cell lines and one normal cell line and found that ZFAS1 was up-regulated in GC cell lines. Furthermore, circulating tumor cells (CTC) were simulated by mixing GC cells with peripheral blood. After EpCAM antibody-based cell sorting, we found that the expression of ZFAS1 was positively correlated with EMT property of CTCs. In GC patient tissue samples, we found that Twist was positively correlated with ZFAS1 by immunohistochemical staining. Taken together, our results suggested that ZFAS1 was up-regulated in both tissues and plasmas of GC patients, and may be involved in regulation of EMT in GC progression. Thus, ZFAS1 might serve as a potential diagnostic marker and/or therapeutic target for GC.

Differential expression of plasma miR-125b in hepatitis B virus related liver diseases and diagnostic potential for hepatitis B virus induced hepatocellular carcinoma.

Acting as a tumor suppressor, microRNA (miR)‐125b shows aberrant low expression in hepatocellular carcinoma (HCC), and researchers have found that its dysregulation has a close relationship with hepatitis B virus (HBV) infection. Here, we investigated the expression profile of this miRNA in the plasma of healthy subjects and patients with chronic HBV‐related liver diseases in order to confirm the feasibility of this circulating miRNA as a differential diagnostic biomarker for HBV‐induced HCC (HBV‐HCC).

Diagnostic Potential of Differentially Expressed Homer1, IL-1β, and TNF-α in Coronary Artery Disease

Increasing evidences suggest that inflammation plays an important role in the pathogenesis of coronary artery disease (CAD). Numerous inflammatory cytokines and related genes mediate adverse cardiovascular events in patients with CAD, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and Homer in the present study. The study was carried out on 163 CAD patients at different stages and 68 controls. The gene expression of Homer1, Homer2, Homer3, IL-1β, and TNF-α in the peripheral blood leukocytes were measured by real-time polymerase chain reaction. The mRNA levels of Homer1, IL-1β, and TNF-α in CAD patients were significantly higher than those in the control group, but not Homer2 and Homer3. However, there was no considerable difference in the mRNA levels of Homer1, IL-1β, and TNF-α among AMI, UAP, and SAP three subgroups of CAD. The receiver operating characteristic (ROC) curves showed that Homer1 had a better diagnostic value for UAP patients compared with IL-1β and TNF-α. Like IL-1β and TNF-α, Homer1 may also be an important participant of atherosclerotic plaque development and eventually rupture. The results of the present study may provide an important basis for diagnosing CAD patients, and provide new therapeutic targets for CAD.

Plasma miR-92a-2 as a biomarker for small cell lung cancer

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in the carcinogenesis and progression of cancers. Aberrant expression of miRNAs in tissue and plasma has been found in various solid tumors. Our research aims to determine whether the abnormal plasma miRNA expression patterns can be used as a predictive marker for the diagnosis and prognosis of small cell lung cancer (SCLC). Fifty SCLC patients and 30 healthy controls annotated with clinical characteristics and specific questionnaire survey for smoking history were available. Quantification of several miRNAs (miR-20a-5p, miR-92a-2-5p and miR-17-5p) was performed using quantitative real-time polymerase chain reaction (qRT-PCR), and results were analyzed using SPSS statistics 17.0. Plasma miR-92a-2 level was significantly higher in the SCLC patients group compared with healthy control (P< 0.0001), the receiver operating characteristic (ROC) curve analysis showed that the specificity and sensitivity were at 100% and 56% for diagnosis of SCLC, area under the ROC curve (AUC) was 0.761. No other statistically significant differences were found in the expression level of plasma miR-92a-2 among survival analysis in SCLC. Detection of miR-92a-2 levels in plasma could be a potential and noninvasive method for the diagnosis of SCLC.

The Circular RNA hsa_circ_0001445 Regulates the Proliferation and Migration of Hepatocellular Carcinoma and May Serve as a Diagnostic Biomarker

Circular RNAs (circRNA), a class of noncoding RNAs, have been found to be involved in various diseases. Here, the expression levels of the circRNA hsa_circ_0001445 in 73 pairs of hepatocellular carcinoma (HCC) and adjacent nontumor tissues were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Our data demonstrate that the hsa_circ_0001445 levels were significantly decreased in HCC tissues (P < 0.001) and markedly associated with the number of tumor foci (P = 0.014). Furthermore, in vitro approaches showed that overexpression of hsa_circ_0001445 promoted apoptosis and inhibited proliferation, migration, and invasion of HCC-derived cells, suggesting that hsa_circ_0001445 might be involved in the development of HCC. In addition, we found that the plasma hsa_circ_0001445 transcription levels in HCC patients were lower than those in cirrhosis (P < 0.001) and hepatitis B (P < 0.001) patients as well as in healthy controls (P < 0.001). In fact, receiver operating characteristic curve analysis indicated that plasma hsa_circ_0001445 could be a fairly accurate marker to distinguish HCC cases from healthy controls as well as patients with cirrhosis or hepatitis B.

Prognostic value of abnormally expressed lncRNAs in ovarian carcinoma: a systematic review and meta-analysis

Ovarian cancer (OC) is the most deadly gynecological cancer and it is urgently needed to find a new marker for the progress of OC. Many long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in ovarian carcinoma, and may serve as prognostic markers. Therefore, we conducted this meta-analysis to gain a better understanding of the prognostic value of lncRNAs in patients with varian carcinoma. We systematically searched PubMed, EMBASE, and Web of Science. A total of 13 eligible studies, including 10 on clinicopathological features, 13 on prognosis were identified. Pooled hazard ratios (HRs) or odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. Our results revealed that the increased expressions of 8 lncRNAs were associated with poor prognosis and the decreased expressions of 5 lncRNAs were related to poor prognosis in ovarian carcinoma. High HOTAIR expression was associated with shorter overall survival in ovarian cancer (pooled HR: 2.05, 95% CI: 1.51-2.77, P < 0.001). In conclusion, our meta-analysis suggested that LncRNAs could function as potential prognostic markers for ovarian cancer patients and high expression HOTAIR was associated with shorter overall survival in ovarian cancer.

Inhibition of miR-155, a therapeutic target for breast cancer, prevented in cancer stem cell formation

BACKGROUND Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. METHODS The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. RESULTS In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. CONCLUSIONS Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer.

Decreased expression of LncRNA SRA1 in hepatocellular carcinoma and its clinical significance

BACKGROUND Hepatocellular carcinoma (HCC), is an extremely aggressive malignancy with poor prognosis and high fatality rates worldwide. Accumulating evidence indicated that novel biomarkers are required to get a better understanding of the biological mechanisms of HCC. SRA1, a long non-coding RNA (lncRNA), serves as a critical regulator in several cancers. However, the association between SRA1 expression and tumorigenesis in HCC tissues remains unclear. OBJECTIVE In the present study, we evaluated the expression of SRA1 in HCC and its clinical association. METHODS The expression levels of SRA1 in 67 pairs of cancer tissues and adjacent normal tissues from HCC patients were detected using quantitative real-time PCR. Expression of SRA1 in HCC cell lines compared with normal human hepatocyte cell lines was also measured. Finally, the potential associations between its level in HCC tissues and the clinicopathological parameters were analyzed as well. RESULTS The results indicated that the expression levels of SRA1 in HCC were remarkably decreased, compared with matched normal tissues (P< 0.001). Levels of SRA1 in HCC cell lines were also significantly decreased than that in normal human hepatocyte cell line L-02. Additionally, the levels of SRA1 were significantly associated with tumor size (P= 0.020) and serum GLU level (P= 0.046). CONCLUSIONS This study highlighted that SRA1 was downregulated in HCC and might serve as a tumor suppressor in HCC, which laid a solid foundation for future research.

Long non-coding RNA XIST predicts worse prognosis in digestive system tumors: a systemic review and meta-analysis

Increasing studies are indicating that long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is associated with the prognosis of cancer patients. However, the results have been disputed. Therefore, we aimed to further explore the prognostic value and clinical significance of XIST in various types of cancers. Then, we focussed our research on the comparison of the predictive value of XIST between digestive system tumors and non-digestive system tumors. We performed a systematic search by looking up PubMed, Embase, Cochrane Library, Web of Science, and Medline (up to 3 January 2018). Fifteen studies which matched our inclusion criteria with a total of 920 patients for overall survival and 867 patients for clinicopathological characteristics were included in this meta-analysis. Pooled hazard ratios (HR) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated to summarize the effects. Our results suggested that high expression levels of XIST were associated with unfavorable overall survival in cancer patients (pooled HR = 1.81, 95% CI: 1.45–2.26). Additionally, we found that XIST was more valuable in digestive system tumors (pooled HR = 2.24, 95% CI: 1.73–2.92) than in non-digestive system tumors (pooled HR = 1.22, 95% CI: 0.60–2.45). Furthermore, elevated expression levels of XIST were connected with distant metastasis and tumor stage. XIST was correlated with poor prognosis, which suggested that XIST might serve as a novel predictive biomarker for cancer patients, especially for patients of digestive system tumors.

Diagnostic Potential of Differentially Expressed Homer1 and Homer2 in Ischemic Stroke.

Background: Ischemic stroke (IS) is an extremely heterogeneous disease with variable pathogenesis. Due to the lack of early diagnostic marker, the mortality rate of IS remains high worldwide. The family of Homer plays an important role in the pathology of atherosclerotic plaque. In this study, we have investigated its expression pattern and clinical significance in IS. Methods: RT-qPCR was performed to detect the expression of Homer1, Homer2, and Homer3. Results: We found that the mRNA levels of Homer1 (p<0.001) and Homer2 (p<0.001), but not Homer3, in large-artery atherosclerosis (LAA) strokes were significantly upregulated than those in non-LAA strokes and controls. Multinomial logistic regression analyses showed that, although none of the Homer was associated with non-LAA strokes, higher Homer1 (adjusted OR=1.337, 95% CI: 1.227-1.458) and Homer2 (adjusted OR=1.099, 95% CI: 1.062-1.138) levels showed significant associations with increased odds of having LAA stroke, compared with the controls. The receiver operating characteristic (ROC) curves showed that the combination of Homer1 and Homer2 had a better diagnostic accuracy to differentiate LAA strokes from non-LAA strokes and controls, and the sensitivity and specificity ratios were 80.5%/90.4% and 98.0%/70.3%, respectively. Conclusion: Our data suggested that Homer1 and Homer2 might be considered as novel diagnostic biomarkers for LAA stroke.