Overexpression of long non-coding RNA RP11-363E7.4 inhibits proliferation and invasion in gastric cancer.

LncRNA RP11-363E7.4 has been shown to be downregulated in gastric cancer (GC), while the effect of lncRNA RP11-363E7.4 on GC and its potential molecular mechanisms is unclear. The purpose of this study was to explore the functional role and underlying molecular mechanisms of lncRNA RP11-363E7.4 involved in GC progress.To address the question, quantitative real-time PCR assay was performed to confirm lncRNA RP11-363E7.4 expression levels in GC tissues and cell lines. Cell proliferation, apoptosis, migration and invasion were estimated using Cell Counting Kit-8, colony formation, scratch wound healing and Transwell assays. Potential molecular mechanisms were evaluated using western blot assay. The results showed that lncRNA RP11-363E7.4 was significantly downregulated in GC cell lines and 82 paired tissues. The correlation between expression and clinicopathological features indicated that low expression of lncRNA RP11-363E7.4 was associated with T stage (P = .010). Functional experiments showed that overexpression of lncRNA RP11-363E7.4 prevented proliferation, migration, and invasion and induced apoptosis of GC cells. Western blot assay revealed that lncRNA RP11-363E7.4 functioned via the p53, Bax/Bcl-2, β-catenin pathway. In summary, this study revealed that lncRNA RP11-363E7.4 functioned as a tumour suppressor by inhibiting proliferation, migration, and invasion and inducing apoptosis of GC cells. Significance of the study:LncRNA RP11-363E7.4 has been shown to be downregulated in GC, while the effect of lncRNA RP11-363E7.4 on GC and its potential molecular mechanism is unclear. We revealed that lncRNA RP11-363E7.4 functioned as a tumour suppressor by inhibiting proliferation, migration, and invasion and inducing apoptosis of GC cells. LncRNA RP11-363E7.4 might become an attractive diagnostic and prognostic biomarker of GC and a promising target for GC treatment.

Chen C ，Wang X ，Liu T ，Tang X ，Liu Y ，Liu T ，Zhu J ... -  《-》

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer.

Recent evidence has shown that some long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory mechanism of lncRNA in gastric cancer (GC) remains unclear. We reannotated the GC gene expression profile into a lncRNA-mRNA biphasic profile and integrated the microRNA target data to construct a global GC triple network. A further clustering and random walk with restart analyses was performed on the triple network from the level of topology analyses. Quantitative real-time PCR was used to determine expression of lncRNA RP11-363E7.4. Kaplan-Meier analyses was performed to evaluate the prognostic value of lncRNA RP11-363E7.4. We constructed a gastric cancer lncRNA-miRNA-mRNA network (GCLMN) including six lncRNAs, 332 mRNAs, and 3,707 edges. For the shared lncRNA RP11-363E7.4, the interacting gene and microRNA functional enrichment studies implied that lncRNA RP11-363E7.4 might function as a new regulator in GC. The expression of lncRNA RP11-363E7.4 was downregulated compared with that of paracarcinoma tissues in five GC samples. High expression of lncRNA RP11-363E7.4 was found to be correlated to better overall survival (OS) for GC patients. This study focused on GC lncRNA-miRNA-mRNA regulatory networks, and found that lncRNA RP11-363E7.4 was a new GC risk lncRNA, which might provide novel insight into a better understanding of the pathogenesis of GC.

Wang P ，Li J ，Zhao W ，Shang C ，Jiang X ，Wang Y ，Zhou B ，Bao F ，Qiao H ... -  《-》

Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis.

Gastric cancer (GC) is a common malignancy with a global incidence that ranks fourth among all tumor types. Epithelial-to-mesenchymal transition (EMT) is a tumor biological process with a role in GC cell metastasis. Long non-coding RNAs (lncRNAs) and microRNAs possess important regulatory functions at the cellular level and in diverse pathophysiological processes. This study was conducted to investigate whether lncRNA RP11-789C1.1 regulates EMT in GC by mediating the miR-5003/E-cadherin pathway. RP11-789C1.1 and miR-5003 expression was detected in GC specimens and cell lines by quantitative real-time PCR. Western blotting and immunohistochemistry were performed to detect EMT markers in GC. Cell Counting Kit 8 assays were carried out to explore cell proliferation. Wound healing and Transwell assays were conducted to determine the migration and invasion of GC cells. To clarify the correlation between RP11-789C1.1, miR-5003, and E-cadherin, dual-luciferase reporter assays were applied. LncRNA RP11-789C1.1 was significantly down-regulated in GC patients and cell lines, along with the concomitant up-regulation of miR-5003. Silencing RP11-789C1.1 and over-expressing miR-5003 significantly promoted the tumor behavior of GC cells. Dual-luciferase reporter assays confirmed that miR-5003 was the target of both RP11-789C1.1 and E-cadherin. Furthermore, at both the mRNA and protein level, silencing RP11-789C1.1 remarkably reduced the expression of E-cadherin and promoted EMT, which were reversed by knocking down miR-5003. LncRNA RP11-789C1.1 inhibited EMT in GC through the RP11-789C1.1/miR-5003/E-cadherin axis, which could be a promising therapeutic target for GC.

Chen Z ，Wu J ，Huang W ，Peng J ，Ye J ，Yang L ，Yuan Y ，Chen C ，Zhang C ，Cai S ，He Y ，Wu S ，Song W ... -  《-》

Long non-coding RNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer.

The present study aimed to investigate the effect of long non-coding RNA (lncRNA) RP11-552M11.4 on cell proliferation, apoptosis, migration and invasion as well as its targeting genes in epithelial ovarian cancer (EOC) cells. LncRNA RP11-552M11.4 expression was detected in 67 tumor tissues and paired adjacent tissues obtained from EOC patients. lncRNA RP11-552M11.4 mimic/inhibitor plasmids were transferred into ovarian cancer cells (SKOV3, A-2780) and normal ovarian epithelial cells (IOSE80 cells). In addition, rescue experiment was carried out by transferring BRCA2 inhibitor&lncRNA RP11-552M11.4 inhibitor plasmids into SKOV3 and A-2780 cells. qPCR, western blot, CKK-8, Annexin V/propidium iodide (AV/PI), wound-healing and Matrigel invasion assays were carried out to detect RNA expression, protein expression, cell proliferation, apoptosis, migration, and invasion, respectively. LncRNA RP11-552M11.4 expression was elevated in tumor tissues compared with paired adjacent tissues and correlated with higher pathological grade, International Federation of Gynecology and Obstetrics stage and worse overall survival in EOC patients. LncRNA RP11-552M11.4 promoted SKOV3 cell proliferation, migration and invasion whereas it inhibited apoptosis. Rescue experiment and luciferase reporter assay showed that lncRNA RP11-552M11.4 regulated SKOV3 cells functions through binding BRCA2. Further experiments in A-2780 cells also validated that lncRNA RP11-552M11.4 induced A-2780 cell proliferation while repressing apoptosis by targeting BRCA2. In addition, upregulation of lncRNA RP11-552M11.4 increased IOSE80 cell proliferation, migration and invasion while decreasing apoptosis. In conclusion, lncRNA RP11-552M11.4 correlates with worse prognosis, and promotes cell proliferation, migration, invasion, and inhibits cell apoptosis by down-regulating BRCA2 in EOC.

Huang K ，Geng J ，Wang J 《-》

DC-SIGN mediates gastric cancer progression by regulating the JAK2/STAT3 signaling pathway and affecting LncRNA RP11-181G12.2 expression.

The molecular mechanisms of gastric cancer (GC) development are very complicated. Recent studies revealed that DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein (DC-SIGNR) is involved in colon cancer and GC biological processes. However, the exact roles of DC-SIGN in GC remain unrevealed. DC-SIGN overexpression and knockdown experiments were performed by using DC-SIGN shRNA or DC-SIGN plasmid to investigate the biological roles of DC-SIGN in proliferation, cell cycle progression, migration and invasion of GC cells in vitro. Furthermore, the lncRNA profiles of SGC-7901 cells with control shRNA and DC-SIGN shRNA were generated by using microarray analysis. Mechanistically, the relationship between DC-SIGN, RP11-181G12.2 and the JAK2/STAT3 signaling pathway was then investigated using qRT-PCR and western blot assays. Additionally, we analyzed DC-SIGN and RP11-181G12.2 expression levels in GC specimens based on the Cancer Genome Atlas database. In this study, the results showed that DC-SIGN was highly expressed in GC cells and significantly correlated with advanced clinical stage and lymphatic metastasis. Downregulation of DC-SIGN significantly inhibited the proliferation, cell cycle progression, migration and invasion of GC cells in vitro. The reverse results could partly be seen with the upregulation of DC-SIGN. Mechanistically, knockdown of DC-SIGN inactivated the JAK2/STAT3 signaling pathway, and overexpression of DC-SIGN activated the JAK2/STAT3 signaling pathway. In addition, through LncPath microarray analysis, we identified a lncRNA, RP11-181G12.2, that was significantly upregulated after knockdown of DC-SIGN; this was also confirmed by qRT-PCR. Furthermore, RP11-181G12.2 knockdown enhanced DC-SIGN expression in GC cells, further activating the JAK2/STAT3 signaling pathway. In contrast, DC-SIGN overexpression suppressed RP11-181G12.2 expression. Our study suggests that DC-SIGN might be involved in the progression of GC by regulating the JAK2/STAT3 signaling pathway and affecting lncRNA RP11-181G12.2 expression.

Li X ，Na H ，Xu L ，Zhang X ，Feng Z ，Zhou X ，Cui J ，Zhang J ，Lin F ，Yang S ，Yue F ，Mousa H ，Zuo Y ... -  《-》