Surgeons usually use synthetic polymer meshes for abdominal wall hernia repair. However, synthetic polymer meshes exhibit a lack of growth and related complications. In this study, we produced a tissue-engineered patch for abdominal hernia repair. Autologous bone-marrow-derived mesenchymal stem cells (BMSCs) were isolated and proliferated in vitro; decellularized dermal scaffolds (DSs) were prepared using enzymatic process; and then BMSCs were seeded onto the DSs for the construction of tissue-engineered patches. Under general anesthesia, rabbits underwent creation of abdominal wall defects and which were repaired with BMSC-seeded DSs, acellular DSs, and skin sutures only, respectively. Animals were sacrificed after 2 months for assessing the histological and gross examination. Abdominal hernias were absent in animals repaired with cell-seeded group, and abdominal hernias or bulges appeared in all animals repaired with acellular group. All the animals that were not repaired died within 10 days. The cell-seeded implants were thicker and indicated good angiogenesis compared with that of the acellular implants, both in histological and gross examination. The tissue-engineered patches prepared with BMSCs seeding on DSs can be used for abdominal wall hernia repair.
Gastric cancer (GC) is a malignant tumour with high lethality. Accruing evidence elucidates the critical adjusting role of long non-coding RNA (lncRNAs) in human cancers. DDX11 antisense RNA 1 (DDX11-AS1) was previously found to be involved in GC pathogenesis. However, the precise molecular mechanisms of DDX11-AS1 need to be further investigated. In this study, we found that DDX11-AS1 expression was up-regulated in GC tumour tissues and cells. Increased DDX11-AS1 expression was associated with advanced TNM stage and lymph node metastasis. Functionally, knockdown of DDX11-AS1 repressed cell proliferation and clone formation, while induced cell cycle arrest and apoptosis. As expected, DDX11-AS1 overexpression displayed the opposite effect. Mechanically, DDX11-AS1 enhanced SPC18 expression through acting as a ceRNA for miR-873-5p. Furthermore, the inhibitory effect of DDX11-AS1 silencing on malignant biological behaviour of GC cells was attenuated by either miR-873-5p inhibitor or SEC11A up-regulation. Moreover, suppression of DDX11-AS1 also decreased GC tumorigenesis in vivo. In conclusion, DDX11-AS1 may serve as an oncogene in GC progression by sponging miR-873-5p and promoting SPC18 expression, providing a new insight into the mechanisms of DDX11-AS1 and elucidating a promising therapy target in GC.
BackgroundAberrant DNA methylation is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor genes and other genes in diverse human cancers. Gastric carcinoma is one of the tumors with a high frequency of aberrant methylation in promoter region. Hence we investigated the promoter methylation status and expression level of HOXA11 gene which may involve in GC development.MethodsThirty-two surgical excised gastric cancer specimens, twelve paired adjacent non-cancerous specimens and seven normal gastric mucosas were examined. The methylation status and expression level of HOXA11 gene were determined by bisulfite sequencing polymerase chain reaction (BSP), real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) respectively. HOXA11 expression was knocked-down with siRNA to mimic HOXA11 gene hypermethylation and ability of cell proliferation and migration was determinate. In addition, we analyzed and correlated the findings with clinicopathological features.ResultsThe methylation level of HOXA11 gene in gastric cancer tissues and adjacent non-cancerous tissues were higher than those in normal gastric mucosa (P < 0.05). The methylation level was higher in TNM III and IV patients of GC than those in TNM I and II patients (P < 0.05). The expression of HOXA11 mRNA and protein decreased in normal gastric mucosa, peri-cancer tissue and GC (P < 0.05). HOXA11 expression was inversely correlated with DNA methylation (P < 0.05). Knocked-down of HOXA11 expression with siRNA in BGC-823 cells enhanced cell proliferation compared with control, but no significant different was observed in migration ability.ConclusionHypermethylation and decreased expression of HOXA11 gene may be involved in the carcinogenesis and development of GC and may provide useful information for the prediction of the malignant behaviors of GC. And the expression of HOXA11 is impaired by DNA methylation. However, repression of HOXA11 expression promoted BGC-823 cell proliferation.
The aim of this study was to investigate the functional role and the underlying molecular mechanism of long noncoding RNA (lncRNA) prostate cancer–associated transcript 1 (PCAT‐1) in cisplatin resistance of gastric cancer (GC). Our results indicated that PCAT‐1 was overexpressed in CDDP‐resistant GC tumor tissues and cell lines. High expression of PCAT‐1 was closely correlated with short overall survival in patients with GC. Downregulation of PCAT‐1 resensitized CDDP‐resistant GC cells to cisplatin. In addition, PCAT‐1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. More importantly, PTEN silencing counteracted PCAT‐1 knockdown–mediated enhancement in cisplatin sensitivity of CDDP‐resistant GC cells. In summary, PCAT‐1 led to cisplatin resistance in GC cells through epigenetically suppressing PTEN expression, providing a novel therapeutic strategy for GC patients with chemoresistance.
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