Qiang Sun

Meta-analysis: the use of carbon dioxide insufflation vs. room air insufflation for gastrointestinal endoscopy

Carbon dioxide (CO2) insufflation has been proposed as an alternative to air insufflation to distend the lumen in gastrointestinal (GI) endoscopy.

Antitumor efficacy of C-X-C motif chemokine ligand 14 in hepatocellular carcinoma in vitro and in vivo.

C‐X‐C motif chemokine ligand 14 (CXCL14) is a novel gene that is expressed in many normal cells but is absent from or expressed at very low levels in cancerous tissues such as head and neck squamous cell carcinoma (HNSCC), prostate cancer, and pancreatic cancer. However, the relationship between CXCL14 and hepatocellular carcinoma (HCC) remains unclear. Therefore, the exact function of CXCL14, which may modulate antitumor immune responses in certain cancers, was evaluated. CXCL14 was downregulated in HCC tissues compared to adjacent normal tissues. Moreover, overexpression of CXCL14 had an inhibitory effect on cell proliferation, induced apoptosis and inhibited the invasion of HCC cells in vitro. Upregulation of CXCL14 by lentivirus also significantly suppressed the growth of subcutaneous tumors in nude mice in vivo. We further demonstrated that the loss of CXCL14 expression was regulated by promoter hypermethylation. CXCL14 induced tumor cell apoptosis through both the mitochondrial and nuclear apoptosis pathways. CXCL14 suppressed tumor cell proliferation through regulation of the cell cycle by downregulation of cyclins and cyclin‐dependent kinases. In conclusion, CXCL14 plays a pivotal role as a potential tumor suppressor in HCC. The re‐expression or upregulation of this gene may provide a novel strategy in HCC therapy in the future.

Genome-wide analysis of long noncoding RNA (lncRNA) expression in colorectal cancer tissues from patients with liver metastasis

The liver is the most frequent site of metastasis in colorectal cancer (CRC), in which long noncoding RNAs (lncRNAs) may play a crucial role. In this study, we performed a genome‐wide analysis of lncRNA expression to identify novel targets for the further study of liver metastasis in CRC. Samples obtained from CRC patients were analyzed using Arraystar human 8 × 60K lncRNA/mRNA v3.0 microarrays chips to find differentially expressed lncRNAs and mRNAs. The results were confirmed by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). The differentially expressed lncRNAs and mRNAs were identified through fold change filtering. Gene ontology (GO) and pathway analyses were performed using standard enrichment computational methods. In the CRC tissues from patients with liver metastasis, 2636 lncRNAs were differentially expressed, including 1600 up‐regulated and 1036 down‐regulated over two‐fold compared with the CRC tissues without metastasis. Among the 1584 differentially expressed mRNAs, 548 were up‐regulated and 1036 down‐regulated. GO and pathway analysis of the up‐regulated and down‐regulated mRNAs yielded different results. The up‐regulated mRNAs were associated with single‐organism process (biological process), membrane part (cellular component), and transporter activity (molecular function), whereas the down‐regulated mRNAs were associated with cellular process, membrane, and binding, respectively. In the pathway analysis, 27 gene pathways associated with the up‐regulated mRNAs and 51 gene pathways associated with the down‐regulated mRNAs were targeted. The significant changes in NQO2 (NM_000904) mRNA and six associated lncRNAs were selected for validation by qRT‐PCR. Aberrantly expressed lncRNAs may play an important role in the liver metastasis of CRC. The further study can provide useful insights into the biology and, ultimately, the prevention of liver metastasis.

The lncRNA HOXA11-AS functions as a competing endogenous RNA to regulate PADI2 expression by sponging miR-125a-5p in liver metastasis of colorectal cancer

Several long non-coding RNAs (lncRNAs) play important roles in the regulation of liver metastasis in colorectal cancer (CRC) patients. We previously described the potential involvement of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), miR-125a-5p, and peptidyl arginine deiminase 2 (PADI2) in promoting liver metastasis in CRC patients. In the present study, we verified the significant upregulation of HOXA11-AS and PADI2, as well as the downregulation of miR-125a-5p, in CRC patients with liver metastasis. Overexpression and knockdown studies of HOXA11-AS or PADI2, as well as gain-/loss-of-function studies of miR-125a-5p, revealed a positive correlation between HOXA11-AS and PADI2 and a negative correlation with miR-125a-5p in the regulation of liver metastasis in CRC cell lines. Overall, we conclude that HOXA11-AS promotes liver metastasis in CRC by functioning as a miR-125a-5p sponge and describe a novel HOXA11-AS–miR-125a-5p–PADI2 regulatory network involved in CRC liver metastasis.

Hepatitis B virus X protein inhibits p53-mediated upregulation of mitofusin-2 in hepatocellular carcinoma cells.

The hepatitis B virus X (HBx) protein has many significant roles in hepatocellular carcinoma (HCC). Our previous research demonstrated that mitofusion-2 (Mfn2), a potential tumor suppressor gene in HCC, is a novel direct target of p53 that exerts apoptotic effects via the mitochondrial apoptotic pathway. However, the relationship between HBx and Mfn2 expression in the development of HCC is unknown. We found that HBx had little direct effect on the expression of Mfn2 or p53 in HCC cells not treated with doxorubicin. However, HBx inhibited the upregulation of Mfn2 in HBx-transfected HCC cells simultaneously treated with doxorubicin or cotransfected with p53 plasmid, as evidenced by Western Blot and real-time PCR. Through electrophoretic mobility shift analysis, we confirmed that HBx interfered with the binding event of the p53 protein and the p53 binding site-oligo of the Mfn2 promoter. Moreover, luciferase assays revealed that the activity of the Mfn2 promoter did not increase when transfected with HBx plasmid in doxorubicin-treated HepG2 cells. These results indicate that HBx impacts p53-mediated transcription of Mfn2, providing insight into the negative effect of HBx against p53-dependent chemotherapeutic agents, such as doxorubicin, used in the treatment of HCC.

Expression and Clinical Significance of the Novel Long Noncoding RNA ZNF674-AS1 in Human Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) play crucial roles in cancer occurrence and progression. However, the relationship between the expression levels of lncRNAs and the hepatocellular carcinoma (HCC) process is unclear. The goal of this study was to determine the expression level of ZNF674-AS1, a newly found lncRNA, in HCC and its clinical association. The expression of ZNF674-AS1 in 137 pairs of tumorous and adjacent normal tissues from patients with HCC was detected by quantitative real-time reverse transcription polymerase chain reaction. Additionally, the potential associations between its level in HCC tissue and clinicopathological features were analyzed. The expression of ZNF674-AS1 in the HCC cell lines HepG2, HCCLM3, SK-Hep1, HuH7, Hep3B, and MHCC97H was significantly downregulated compared with that in the normal liver cell line QSG-7701. The expression of ZNF674-AS1 was downregulated in 72% (99/137) of HCC tissues compared with that in paired adjacent normal tissues (p < 0.01). The results showed that the ZNF674-AS1 expression level was significantly correlated with metastasis (p = 0.041), clinical stage (p = 0.039), and histopathologic grading (p = 0.045). In addition, the Kaplan–Meier survival curves revealed that low ZNF674-AS1 expression was associated with poor prognosis in patients with HCC. Our data suggest that ZNF674-AS1 may play some role during cancer occurrence and progression and may be a new biomarker for HCC.

miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer

Improvements in survival rates for pancreatic cancer have been slow and the morality rate continues to increase in patients. MicroRNA (miR)-448 is reported to be significantly downregulated in several types of cancer. In this study, Rab2B is target of miR-488 was confirmed by bioinformatics analysis and validated using a luciferase reporter assay. A total of 72 cases of pancreatic cancer in patients diagnosed at The First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China) were enrolled, and cancer specimens and their adjacent normal tissues were collected for analysis. The expression levels of miR-448 and Rab2B in these tissues and in pancreatic cancer cell lines were quantified using reverse transcription-polymerase chain reaction analysis. miR-448 overexpression was achieved by cell transfection. Protein expression was assessed using western blot analysis. Cell viability, cell cycle and apoptosis were analyzed using CCK-8 assay and flow cytometry, respectively. The results revealed a negative correlation between miR-448 and Rab2B in the pancreatic tissues and cell lines. The results of bioinformatics analysis indicated that miR-448 directly targeted Rab2B. Aberrant miR-448 levels in PANC-1 cells downregulated the expression of Rab2B, and significantly decreased cell proliferation and promoted apoptosis of cancer cells. It was also found that miR-448 mimics resulted in G0/G1 cell cycle arrest and affected the expression of cell cycle regulators, including cyclin D1, p21 and p27. In addition, the miR-448 mimics led to inactivation of the Akt/Mammalian target of rapamycin signaling pathway. The miR-448 mimics induced apoptosis and activated the expression of caspase-3, caspase-9 and poly(ADP-ribose) polymerase. The results suggested that miR-448 was a negative regulator of Rab2B and promoted cell cycle arrest and apoptosis in pancreatic cancer.

Pancreatoduodenectomy combined with portal-superior mesenteric vein resection and reconstruction with interposition grafts for cancer: a meta-analysis

The use of interposition grafts for portal-superior mesenteric vein (PV-SMV) reconstruction during pancreatoduodenectomy (PD) with venous resection (VR) for localized periampullary tumors is a controversial topic. The present meta-analysis aimed to evaluate the perioperative and long-term outcomes in patients who received interposition grafts for PV-SMV reconstruction after PD with VR. The correlative databases were systematically searched to identify relevant trials comparing vein grafts versus no vein grafts during PD with VR. 14 studies including 257 patients with vein grafts and 570 patients without vein grafts were extracted. The meta-analysis indicated no difference in perioperative morbidity, mortality, or thrombosis between the two groups, but the vein graft group was associated with a significantly increased venous thrombosis rate (≥ 6 months) (odds ratio [OR] = 2.75; 95% confidence interval [CI], 1.32–5.73; P = .007). The autologous vein group subgroup analysis also revealed a significantly increased vein thrombosis rate (OR = 3.13; 95% CI, 1.45–6.76; P = .004) between the two groups. Meanwhile, the prosthetic vein group subgroup analysis indicated no difference. Additionally, the oncological value of vein grafts during PD for pancreatic cancer survival was analyzed and revealed no difference in 1-year, 3-year, or 5-year survival between the two groups. Using interposition grafts for PV-SMV reconstruction is safe and effective, and has perioperative outcomes and long-term survival rates compared to those with no vein grafts during PD with VR. However, the lower long-term vein patency rate in patients with vein grafts indicate that interposition grafts may be more likely to lose function.

Overexpression of β3 Chains of Laminin-332 is Associated With Clinicopathologic Features and Decreased Survival in Patients With Pancreatic Adenocarcinoma

Background:Laminin-332 (LM-332, formerly termed laminin-5) is a heterotrimeric glycoprotein that promotes cellular adhesion and migration. The heterotrimer consists of an &agr;3, a &bgr;3, and a &ggr;2 chain. The aim of this investigation was to clarify the clinicopathologic significance of laminin-332&bgr;3 (LN&bgr;3) chain expression and determine its influence on survival in pancreatic ductal adenocarcinoma. Materials and Methods:Quantitative real-time polymerase chain reaction was used to validate and detect the expression of LN&bgr;3 mRNA in 37 pancreatic carcinoma tissue specimens and non-neoplastic pancreatic tissue samples. In addition, the protein expression of LN&bgr;3 was detected by immunohistochemistry methods in 96 pancreatic carcinoma specimens and 90 non-neoplastic pancreatic tissues. We analyzed the association between immunohistochemically detected LN&bgr;3 expression in pancreatic ductal adenocarcinoma and clinicopathologic characteristics. Survival curves were completed using the Kaplan-Meier method and compared using log-rank analysis. Results:Quantitative real-time polymerase chain reaction indicated that the relative value of LN&bgr;3 mRNA was 1.427±1.554 and 1.423±1.439 by 2−&Dgr;(&Dgr;Ct) in pancreatic carcinoma and non-neoplastic pancreatic tissues, respectively, values that were not statistically associated (P=0.991). Immunostaining for LN&bgr;3 was expressed in all patients with pancreatic ductal adenocarcinoma. LN&bgr;3 expression was related to differentiation (P=0.000) and advanced stage (P=0.034). Tumors with low expression of LN&bgr;3 had a survival advantage compared with tumors that had high expression of LN&bgr;3 (P=0.016). Multivariate analysis indicated that location is an independent predictor of overall survival, whereas other clinicopathologic characteristics such as tumor size, duodenal invasion, differentiation, extent of invasion, hepatic metastasis, and expression of LN&bgr;3 were not. Conclusion:Our results suggest that LN&bgr;3 expression may play a key role in the progression and prognosis of pancreatic ductal adenocarcinoma.