Haojun Song

Long non-coding RNA expression profile in human gastric cancer and its clinical significances.

BackgroundLong non-coding RNAs (lncRNAs) are prevalently transcribed in the genome yet their potential roles in human cancers are not well understood. The aim of the present study was to determine the lncRNA expression profile in gastric cancer and its potential clinical value.MethodsThe global lncRNA expression profile in gastric cancer was measured by lncRNA microarray. Levels of two representative lncRNAs, H19 and uc001lsz, were confirmed by real-time reverse transcriptase-polymerase chain reaction. The relationship between their levels and clinicopathological factors of patients with gastric cancer was explored. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases.ResultsTotal of 135 lncRNAs, which differential expression levels between tumor and non-tumorous tissues were more than twofold, were found (GEO No. GSE47850). The most down-regulated lncRNAs in gastric cancer tissues were FER1L4, uc001lsz, BG491697, AF131784, uc009ycs, BG981369, AF147447, HMlincRNA1600, and AK054588; while the most up-regulated ones were H19, HMlincRNA717, BM709340, BQ213083, AK054978, and DB077273. H19 was found highly expressed in stomach and liver cancer cell lines, while lowly expressed in lung cancer and prostate cancer cell lines. Uc001lsz was lowly expressed in gastric, lung and liver cancer cell lines, while highly expressed in prostate cancer. The areas under ROC curves were up to 0.613, 0.751, and 0.761 for H19, uc001lsz, and the combination, respectively.ConclusionsThe lncRNA expression profile in gastric cancer suggests the potential roles of lncRNAs in gastric cancer occurrence and development. The overexpression of H19 in gastric cancer suggests that H19 may be participated in gastric cancer. The reduced expression of uc001lsz in gastric cancer cell lines and tissues, its associations with TNM stage, and its dysregulation in early cancer and precancerous lesions suggest that uc001lsz may be a potential marker for the diagnosis of early gastric cancer.

MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer

The epigenetic regulation of microRNAs is one of several mechanisms underlying carcinogenesis. We found that microRNA-195 (miR-195) and microRNA-378 (miR-378) were significantly down-regulated in gastric cancer tissues and gastric cancer cell lines. The expression of miR-195 and miR-378 in gastric cancer cells was significantly restored by 5-aza-dC, a demethylation reagent. The low expression of miR-195 and miR-378 was closely related to the presence of promoter CpG island methylation. Treatment with miR-195/miR-378 mimics strikingly suppressed the growth of gastric cancer cells whereas promoted the growth of normal gastric epithelial cells. In contrast, administration of miR-195/miR-378 inhibitors significantly prevented the growth of normal gastric epithelial cells. Expression of cyclin-dependent kinase 6 and vascular endothelial growth factor was down-regulated by exogenous miR-195 and miR-378, respectively. In conclusion, miR-195 and miR-378 are abnormally expressed and epigenetically regulated in gastric cancer cell lines and tissues via the suppression of CDK6 and VEGF signaling, suggesting that miR-195 and miR-378 have tumor suppressor properties in gastric cancer.

Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer

MicroRNAs (miRNAs) play a crucial role in carcinogenesis; however, it largely remains unclear whether miRNAs in gastric juice, which is specific for gastric tissues, can be used as biomarkers for gastric cancer. The objective of the current study was to investigate the feasibility of using gastric juice miRNAs as potential biomarkers to assist in screening for gastric cancer.

Decreased expression of long noncoding RNA AC096655.1-002 in gastric cancer and its clinical significance.

Long noncoding RNAs (lncRNAs) are newfound noncoding RNAs that are greater than 200 nucleotides in length. They have emerged recently as major players in governing fundamental biological processes. However, the expression level of lncRNAs and their clinical significances are not well understood. To investigate the lncRNA expression in gastric cancer, real-time reverse transcriptase-polymerase chain reaction was conducted. Then, the association between the level of AC096655.1-002, one of lncRNA, in gastric cancer tissues and the clinicopathological features of patients with gastric cancer was further analyzed. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values. The results showed that AC096655.1-002 was significantly downregulated in gastric cancer tissues compared with paired adjacent non-tumorous tissues (P < 0.001). Its expression level was significantly correlated with lymph node metastasis (P < 0.001), distant metastasis (P < 0.001), tumor–node–metastasis stages (P < 0.001), and differentiation (P = 0.030). The area under the ROC curve of AC096655.1-002 was up to 0.731. For the detection of gastric cancer, the use of AC096655.1-002 showed a remarkable improvement compared with the use of serum carcinoembryonic antigen. These results indicated that lncRNA AC096655.1-002 may be a potential biomarker in the diagnosis of gastric carcinoma.

Growth inhibitory effects of three miR-129 family members on gastric cancer

Reduced expression of microRNA-129 (miR-129) has been reported in several types of tumor cell lines as well as in primary tumor tissues. However, little is known about how miR-129 affects cell proliferation in gastric cancer. Here, we show that all miR-129 family members, miR-129-1-3p, miR-129-2-3p, and miR-129-5p, are down-regulated in gastric cancer cell lines compared with normal gastric epithelial cells. Furthermore, using the real-time cell analyzer assay to observe the growth effects of miR-129 on gastric cancer cells, we found that all three mature products of miR-129 showed tumor suppressor activities. To elucidate the molecular mechanisms underlying down-regulation of miR-129 in gastric cancer, we analyzed the effects of miR-129 mimics on the cell cycle. We found that increased miR-129 levels in gastric cancer cells resulted in significant G0/G1 phase arrest. Interestingly, we showed that cyclin dependent kinase 6 (CDK6), a cell cycle-associated protein involved in G1-S transition, was a target of miR-129. We also found that expression of the sex determining region Y-box 4 (SOX4) was inversely associated with that of miR-129-2-3p and miR-129-5p but not of miR-129-1-3p. Together, our data indicate that all miR-129 family members, not only miR-129-5p, as previously thought, play an important role in regulating cell proliferation in gastric cancer.

lncRNA-AC130710 targeting by miR-129-5p is upregulated in gastric cancer and associates with poor prognosis

Long noncoding RNAs (lncRNAs) play an important role in cancer occurrence and development. However, there is largely unknown about lncRNAs significance in the diagnosis and treatment of gastric cancer. In our study, we focused on AC130710, one of lncRNAs. Gastric cancer tissues and adjacent tissues were gathered from 78 patients with gastric cancer. The AC130710 levels were detected by reverse transcription polymerase chain reaction (RT-PCR). Then, we further analyzed the association between AC130710 level and the clinicopathological factors of patients with gastric cancer. Finally, the molecular mechanism underling AC130710 highly expressed in gastric cancer cells was explored. The results showed that AC130710 in cancer tissues from patients with gastric cancer was significantly higher than those in adjacent noncancerous tissues (P < 0.05). Its expression level was significantly associated with tumor size (P = 0.013), tumor-node-metastasis (TNM) stages (P = 0.030), and distal metastasis (P = 0.018). AC130710 expression in MGC-803 was significantly higher than that in normal gastric mucosa cell line GES-1 (P < 0.001). Moreover, miR-129-5p may play an important role in the downregulation of AC130710 in gastric cancer cells. These results indicated that lncRNA-AC130710 may be a potential tumor marker for gastric cancer prognosis.

The functional sites of miRNAs and lncRNAs in gastric carcinogenesis

Gastric cancer is one of the most common malignant diseases and has one of the highest mortality rates worldwide. Its molecular mechanisms are poorly understood. Recently, the functions of non-coding RNAs (ncRNAs) in gastric cancer have attracted wide attention. Although the expression levels of various ncRNAs are different, they may work together in a network and contribute to gastric carcinogenesis by altering the expression of oncogenes or tumor suppressor genes. They affect the cell cycle, apoptosis, motility, invasion, and metastasis. Dysregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), including miR-21, miR-106, H19, and ANRIL, directly or indirectly regulate carcinogenic factors or signaling pathways such as PTEN, CDK, caspase, E-cadherin, Akt, and P53. Greater recognition of the roles of miRNAs and lncRNAs in gastric carcinogenesis can provide new insight into the mechanisms of tumor development and identify targets for anticancer drug development.

Long non-coding RNA profiling in laryngeal squamous cell carcinoma and its clinical significance: potential biomarkers for LSCC.

Long non-coding RNAs (lncRNAs) are novel transcripts that may play important roles in cancer. Our study aimed to resolve the lncRNA profile of larynx squamous cell carcinoma (LSCC) and to determine its clinical significance. The global lncRNA expression profile in LSCC tissues was measured by lncRNA microarray. Distinctly expressed lncRNAs were identified and levels of AC026166.2-001 and RP11-169D4.1-001 lncRNAs in 87 LSCC samples and paired adjacent normal tissue were analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The clinical significance of these lncRNAs in laryngeal cancer was analyzed and survival data were estimated by the Kaplan–Meier method and the log-rank test. A receiver operating characteristic (ROC) curve was constructed to check the diagnostic value. In the lncRNA expression profile of tumor samples, 684 lncRNAs were upregulated and 747 lncRNAs were downregulated (fold-change >2.0). Of these, AC026166.2-001 and RP11-169D4.1-001 were distinctly dysregulated, with AC026166.2-001 exhibiting lower expression in cancer tissues and RP11-169D4.1-001 higher expression. We verified that both AC026166.2-001 and RP11-169D4.1-001 were expressed at a lower level in cervical lymph nodes compared with paired laryngeal cancer tissues and paired normal tissues. RP11-169D4.1-001 levels were positively correlated with lymph node metastasis (P = 0.007). From the survival analysis, decreased levels of AC026166.2-001 and RP11-169D4.1-001 were associated with poorer prognosis. The area under the ROC curve was up to 0.65 and 0.67, respectively, and the cut-off point of ΔCt was 11.23 and 10.53, respectively. AC026166.2-001 and RP11-169D4.1-001 may act as novel biomarkers in LSCC and may be potential therapeutic targets for LSCC patients. Both AC026166.2-001 and RP11-169D4.1-001 could be independent prognostic factors for survival in LSCC.

Nurse Participation in Colonoscopy Observation versus the Colonoscopist Alone for Polyp and Adenoma Detection: A Meta-Analysis of Randomized, Controlled Trials

The role of nurse participation (NP) in colonoscopy observation for polyp and adenoma detection is unclear. This study aimed to evaluate whether nurse participation can improve polyp and adenoma detection. Patients and Methods. The PUBMED, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) published in English. The outcome measurements included (1) the polyp and adenoma detection rate (PDR and ADR); (2) the advanced lesions detection rate; and (3) the mean polyp and adenoma detection rate per colonoscopy. Results. Three RCTs with a total of 1676 patients were included. The pooled data showed a significantly higher ADR in the NP group than colonoscopist alone (CA) (45.7% versus 39.3%; RR 1.16; 95% CI, 1.04–1.30). And it showed no significant difference in the PDR and advanced lesions detection rate between the two groups (RR: 1.14, 95% CI: 0.95–1.37; RR: 1.35, 95% CI: 0.91–2.00; resp.). Conclusions. Nurse participation during a colonoscopy can improve the ADR, whereas no benefit for the PDR and advanced lesions detection rate was observed. All RCTs included in the meta-analysis had high risk of bias. Thus, there is a need for new research that uses sound methodology to definitively address the research question under study.

The clinical value of ncRNAs in gastric cancer: a systematic review and meta-analyses.

In recent years, an increasing number of non-coding RNAs (ncRNAs) containing microRNAs (miRNAs), PIWIinteracting RNAs (piRNAs), and long non-coding RNAs (lncRNAs) have been proven to have great potential clinical value in gastric cancer (GC). Moreover, the application of ncRNAs involves many aspects of GC evaluation, from risk prediction [1] to the assessment of clinicopathological features [2] to diagnosis and prognosis [3]. Perhaps, in the near future, ncRNAs may also be used as targets for anticancer drug development [4]. Many researchers have published findings with varied results, but which ncRNA has the greatest value or is the most suitable? How should we use them, singly or jointly? Due to the limitations of sample size and research programs, a single study may not reflect the answers accurately and sufficiently. Therefore, systematic analyses of these data may be valuable for finally determining the potential clinical value of ncRNAs in GC. Furthermore, metaanalyses can enhance the credibility of associated studies by combining data from individual studies and drawing a more comprehensive conclusion. In this paper, we mainly discuss our findings from the following three aspects: clinicopathological features, diagnosis, and prognosis.