The Third Peoples Hospital Of Nantong City

Nantong, China

The Third Peoples Hospital Of Nantong City

Nantong, China

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Chen L.,The Third Peoples Hospital Of Nantong City | Guan H.,The Third Peoples Hospital Of Nantong City | Gu C.,The Third Peoples Hospital Of Nantong City | Cao Y.,The Third Peoples Hospital Of Nantong City | And 2 more authors.
Tumor Biology | Year: 2015

Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor–node–metastasis (TNM) stage. Kaplan–Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC. © 2015 International Society of Oncology and BioMarkers (ISOBM)


Chen L.,The Third Peoples Hospital Of Nantong City | Chu F.,The Sixth Peoples Hospital Of Nantong City | Cao Y.,The Third Peoples Hospital Of Nantong City | Shao J.,The Third Peoples Hospital Of Nantong City | Wang F.,Nantong University
Tumor Biology | Year: 2015

Previous studies have identified a number of microRNAs (miRNAs) that were aberrantly expressed in hepatocellular carcinoma (HCC) tissues. Nevertheless, their diagnostic and prognostic value in serum has not been fully evaluated. Herein, the levels of five serum miRNAs, namely, miR-182, miR-331-3p, miR-197, miR-492, and miR-581, were detected in 103 HCC patients, 95 benign liver diseases, and 40 healthy controls using real-time PCR technique. The results showed that, compared with benign liver diseases and healthy controls, the levels of serum miR-182 and miR-331-3p were significantly increased in HCC patients, both P < 0.001. Area under the receiver–operating characteristic (ROC) curves for serum miR-182 and miR-331-3p were 0.911 (95 % CI, 0.863–0.947) and 0.890 (95 % CI, 0.838–0.930), the sensitivity were 78.6 and 79.61 %, and the specificity were 91.58 and 86.32 %, respectively. Moreover, the combination of serum miR-182, miR-331-3p, and alpha-fetoprotein (AFP) can markedly increase the differential diagnostic value of benign and malignant liver diseases, especially better than serum AFP alone, P < 0.05. Serum miR-182 was positively correlated with serum AFP (P = 0.001), tumor size (P = 0.013), and TNM classification of malignant tumors (TNM) stage (P = 0.003); however, only TNM stage was demonstrated a significant correlation with serum miR-331-3p (P = 0.006). In addition, Kaplan–Meier survival curve, together with univariate and multivariate Cox proportional hazard analyses, further disclosed that serum miR-182 and miR-331-3p were associated with postoperative survival of HCC patients, and both of them were regarded to be independent prognostic factors for patients with HCC. Taken together, our present study indicates that serum miR-182 and miR-331-3p, upregulated in HCC, can provide positive diagnostic and prognostic values for HCC. © 2015, International Society of Oncology and BioMarkers (ISOBM).


PubMed | The Third Peoples Hospital of Nantong City and Nantong University
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.


PubMed | The Sixth Peoples Hospital of Nantong City, The Third Peoples Hospital of Nantong City and Nantong University
Type: Comparative Study | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2015

Previous studies have identified a number of microRNAs (miRNAs) that were aberrantly expressed in hepatocellular carcinoma (HCC) tissues. Nevertheless, their diagnostic and prognostic value in serum has not been fully evaluated. Herein, the levels of five serum miRNAs, namely, miR-182, miR-331-3p, miR-197, miR-492, and miR-581, were detected in 103 HCC patients, 95 benign liver diseases, and 40 healthy controls using real-time PCR technique. The results showed that, compared with benign liver diseases and healthy controls, the levels of serum miR-182 and miR-331-3p were significantly increased in HCC patients, both P<0.001. Area under the receiver-operating characteristic (ROC) curves for serum miR-182 and miR-331-3p were 0.911 (95 % CI, 0.863-0.947) and 0.890 (95 % CI, 0.838-0.930), the sensitivity were 78.6 and 79.61 %, and the specificity were 91.58 and 86.32 %, respectively. Moreover, the combination of serum miR-182, miR-331-3p, and alpha-fetoprotein (AFP) can markedly increase the differential diagnostic value of benign and malignant liver diseases, especially better than serum AFP alone, P<0.05. Serum miR-182 was positively correlated with serum AFP (P=0.001), tumor size (P=0.013), and TNM classification of malignant tumors (TNM) stage (P=0.003); however, only TNM stage was demonstrated a significant correlation with serum miR-331-3p (P=0.006). In addition, Kaplan-Meier survival curve, together with univariate and multivariate Cox proportional hazard analyses, further disclosed that serum miR-182 and miR-331-3p were associated with postoperative survival of HCC patients, and both of them were regarded to be independent prognostic factors for patients with HCC. Taken together, our present study indicates that serum miR-182 and miR-331-3p, upregulated in HCC, can provide positive diagnostic and prognostic values for HCC.

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