Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5′-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.
Previous studies have demonstrated that microRNAs (miRs) are involved in the carcinogenesis of colorectal cancer (CRC). To the best of our knowledge, the function and regulatory role of miR-532-5p in human CRC remains unknown. The aim of the present study was to determine the role and regulation of miR-532-5p in CRC. Using the reverse transcription-quantitative polymerase chain reaction, it was demonstrated that miR-532-5p was upregulated, whereas runt-related transcription factor 3 (RUNX3) was downregulated in CRC tissues. The upregulated miR-532-5p was associated with the downregulated RUNX3. Furthermore, the two biomarkers were associated with numerous clinicopathological characteristics of CRC, including tumor stage, lymph node involvement, differentiation, vessel invasion and tumor recurrence. The luciferase reporter assay demonstrated that transfection with miR-532-5p mimic markedly downregulated the RUNX3 mRNA and protein levels, via specific binding to the 5'-untranslated region of in human HT-29 CRC cells. In addition, an MTT assay and a colony formation assay demonstrated that miR-532-5p overexpression led to increased tumor cell viability and colony formation ability of HT-29 cells. In conclusion, the results of the present study indicate that miR-532-5p may function as an oncogenic miRNA by promoting cell growth in human CRC cells, and such promotion is associated with the targeted inhibition of RUNX3.
BackgroundThe RNA-seq FPKM data of 331 colorectal adenocarcinoma samples in The Cancer Genome Atlas database with matching clinical data were analyzed in order to reveal the prognostic value of m6A RNA methylation regulators in colon adenocarcinoma.Material/MethodsThe expression of 13 m6A RNA methylated regulators in samples were analyzed. The samples were classified into Cluster I and II by consistent clustering. The gene distribution was analyzed by principal component analysis. Further functional analysis of selected m6A RNA genes was performed and potential risk characteristics was developed using Lasso Cox regression algorithm. Using minimum criteria, the risk coefficients of YTHDF1 and HNRNPC were detected for Cluster II. Patients were divided into high-risk and low-risk subgroups based on the risk characteristics. The clinical data were analyzed by univariate and multivariate Cox regression analysis.ResultsExpression of the detected m6A RNA methylated regulators except YTHDC2 in tumors were significantly different from their adjacent mucosa. Among them, only ALKBH5 and METTL4 were downregulated in tumors. The gene distribution between the 2 subgroups were different. The expression of m6A RNA methylation regulators including YTHDF1, HNRNPC, YTHDC2, YTHDC1, ZC3H13, and RBM15 were different between the 2 groups (P<0.05). The prognostic characteristics between the high-risk and low-risk groups were significant different (P<0.05), which had a good predictive significance of prognosis area under the curve (AUC)=0.62). Risk scores were less than 0.05, suggesting risk score was an independent prognostic factor for colon adenocarcinoma.Conclusionsm6A RNA methylation regulators YTHDF1 and HNRNPC can be used as prognostic factors of colon cancer, which has potential value for colon cancer treatment.
Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.
This study aimed to investigate the role of circ0106714-miR-942-5p-discs large homolog 2 (DLG2), a novel interactome, in colorectal cancer (CRC). Circ0106714 was found to be the most significantly downregulated circular RNA in CRC using a bioinformatics method, and we researched whether the ability of circ0106714 to sponge miR-942-5p and release DLG2 could affect CRC development via Hippo-YES-associated protein (YAP) signaling. We first employed qRT-PCR and immunoblotting to detect messenger RNA (mRNA) and protein expression, respectively. Live imaging of mice tumor xenografts was then conducted to study the effect of circ0106714 on tumor progression in vivo. Reporter gene assays were subsequently conducted to verify the predicted targeting relationship between circ0106714, miR-942-5p, and DLG2 mRNA in SW480 and HCT116 cell lines. As well as using flow cytometry for both apoptosis and cell cycle profile analyses, CCK-8 and clone foci formation assays were performed to assess cell survival. Wound healing assay and transwell invasion assay were later carried out to evaluate the migration and invasion of the cell lines. Findings revealed that circ0106714 and DLG2 were significantly downregulated, while miR-942-5p was significantly upregulated in human CRC tissues and cell lines. However, circ0106714 upregulation significantly suppressed tumor progression in vivo and inhibited the malignancy phenotypes of tumor cells in vitro by targeting miR-942-5p. Also discovered in this research was that miR-942-5p could directly target DLG2 mRNA, thus enhancing the malignancy phenotypes of CRC cells. We even found that DLG2 overexpression resulted in enhanced phosphorylation of YAP, a critical downstream effector of DLG2. This downstream effector was demonstrated to have a tumor-suppressive capacity in CRC cell lines. In sum, circ0106714 could suppress CRC by sponging miR-942-5p and releasing DLG2, thus promoting YAP phosphorylation.
The serum and glucocorticoid inducible protein kinase (SGK) family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase (PI3K) signalling pathway. They regulate a range of fundamental cellular processes such as cell proliferation and survival, thereby playing an important role in cancer development. This perspective intends to give an overview on the involvement of SGKs (particularly SGK3) in cancer progression, and compares the actions of SGK3 and AKT in cell cycle regulation, oncogenic signalling, and the potential as a therapeutic target for cancer.
PurposeThis study aimed to evaluate the short- and long-term outcomes of laparoscopic hepatectomy (LH) for colorectal liver metastases (CRLM) in elderly patients.Patients and methodsBetween January 2009 and January 2016, LH was performed for 241 consecutive patients who were ≥60 years old and had CRLM. Based on their age at the LH, the patients were divided into an elderly group (≥70 years old, 78 patients) and a middle-aged group (60–69 years old, 163 patients). The short- and long-term outcomes were compared between the two groups.ResultsCompared to the middle-aged group, the elderly group had higher values for Charlson comorbidity index, proportion of preoperative chemotherapy, and American Society of Anesthesiologists score. No other significant differences were observed in the preoperative characteristics. The elderly group had a higher conversion rate, compared to the middle-aged group, although no significant differences were observed in the surgical procedures, surgical times, intraoperative blood losses, numbers and severities of postoperative 90-day complications, postoperative 90-day mortality rates, pathology results, and other short-term outcomes. Long-term follow-up revealed similar rates of recurrence, disease-free survival, and overall survival in the two groups. Multivariable analysis revealed that age did not independently predict overall survival or disease-free survival.ConclusionSimilar short- and long-term outcomes were observed after LH for CRLM in elderly and middle-aged patients. Thus, advanced age is not a contraindication for LH treatment in this setting.
Background: Colon adenocarcinoma (COAD) is one of the common gastrointestinal malignant diseases, with high mortality rate and poor prognosis due to delayed diagnosis. This study aimed to construct a prognostic prediction model for patients with colon adenocarcinoma (COAD) recurrence. Methods: Differently expressed RNAs (DERs) between recurrence and non-recurrence COAD samples were identified based on expression profile data from the NCBI Gene Expression Omnibus (GEO) repository and The Cancer Genome Atlas (TCGA) database. Then, recurrent COAD discriminating classifier was established using SMV-RFE algorithm, and receiver operating characteristic curve was used to assess the predictive power of classifier. Furthermore, the prognostic prediction model was constructed based on univariate and multivariate Cox regression analysis, and Kaplan-Meier survival curve analysis was used to estimate this model. Furthermore, the co-expression network of DElncRNAs and DEmRNAs was constructed followed by GO and KEGG pathway enrichment analysis. Results: A total of 54 optimized signature DElncRNAs were screened and SMV classifier was constructed, which presented a high accuracy to distinguish recurrence and non-recurrence COAD samples. Furthermore, six independent prognostic lncRNAs signatures (LINC00852, ZNF667-AS1, FOXP1-IT1, LINC01560, TAF1A-AS1, and LINC00174) in COAD patients with recurrence were screened, and the prognostic prediction model for recurrent COAD was constructed, which possessed a relative satisfying predicted ability both in the training dataset and validation dataset. Furthermore, the DEmRNAs in the coexpression network were mainly enriched in glycan biosynthesis, cardiac muscle contraction, and colorectal cancer. Conclusions: Our study revealed that six lncRNA signatures acted as an independent prognostic biomarker for patients with COAD recurrence.
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