Development and validation of a nomogram to predict cancer-specific survival of elderly patients with unresected gastric cancer who received chemotherapy.

This investigation aimed to explore the prognostic factors in elderly patients with unresected gastric cancer (GC) who have received chemotherapy and to develop a nomogram for predicting their cancer-specific survival (CSS). Elderly gastric cancer patients who have received chemotherapy but no surgery in the Surveillance, Epidemiology, and End Results Database between 2004 and 2015 were included in this study. Cox analyses were conducted to identify prognostic factors, leading to the formulation of a nomogram. The nomogram was validated using receiver operating characteristic (ROC) and calibration curves. The findings elucidated six prognostic factors encompassing grade, histology, M stage, radiotherapy, tumor size, and T stage, culminating in the development of a nomogram. The ROC curve indicated that the area under curve of the nomogram used to predict CSS for 3, 4, and 5 years in the training queue as 0.689, 0.708, and 0.731, and in the validation queue, as 0.666, 0.693, and 0.708. The calibration curve indicated a high degree of consistency between actual and predicted CSS for 3, 4, and 5 years. This nomogram created to predict the CSS of elderly patients with unresected GC who have received chemotherapy could significantly enhance treatment accuracy.

MiR-597-5p inhibits carcinogenesis and macrophage recruitment in colitis-related colorectal cancer via reducing the expression of CXCL5.

Despite being the subject of multiple cancer studies, nothing is known about miR-597-5p's role in colitis-associated colorectal cancer (CAC). We intend to explore how miR-597-5p influences the growth and development of CAC. In order to construct a CAC model, mice were stimulated with azoxymethane (AOM)/dextran sulfate sodium (DSS). The in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) was used for the detection of miR-597-5p expression. The protein expression of CXCL5 was determined by western blotting, immunohistochemistry and enzyme-linked immuno sorbent assay (ELISA). The histologic colitis score and hematoxylin and eosin (HE) staining were used to evaluate degree of damage to colonic tissues. The proportion of macrophages detected in colon tumors was also measured using flow cytometry. The transwell test was employed to assess macrophage migration. It was found that the miR-597-5p and its target CXCL5 had a negative correlation. MiR-597-5p expression was decreased, while CXCL5 expression was raised in CAC tissues. In AOM/DSS-induced mice, miR-597-5p deficiency in intestinal epithelial cells resulted in decreasing colon length as well as increasing tumor numbers and histologic colitis score, which was reversed by CXCL5 inhibition. MiR-597-5p deficiency facilitated macrophage recruitment in AOM/DSS-induced mice and promoted macrophage migration in vitro, which were reversed by CXCL5 inhibition. Deficiency of miR-597-5p aggravated macrophage recruitment and tumorigenesis in a mouse CAC model, suggesting that miR-597-5p agonists may have an anti-inflammatory therapeutic effect in inflammatory bowel diseases and reduce the risk of developing CAC.

Molecular Mechanism of Circ_0088300-BOLL Interaction Regulating Mitochondrial Metabolic Reprogramming and Involved in Gastric Cancer Growth and Metastasis.

This study aims to investigate the effect and molecular mechanism of the interaction between circRNA circ_0088300 and the RNA binding protein (RBP) BOLL on the growth and metastasis of gastric cancer. A prognostic risk model was established by screening differentially expressed RBP genes from the TCGA database, and BOLL was identified as a critical RBP. Gene Set Enrichment analysis (GSEA) showed that BOLL was associated with mitochondrial function. The upregulation fold change of circ_0088300 was the highest in the GSE93541 data set, and the RPISeq database confirmed its binding relationship with BOLL. In vitro experiments showed that BOLL regulates mitochondrial metabolism and cancer cell function and circ_0088300 upregulates the expression level of BOLL. In vivo experiments demonstrated that knocking down circ_0088300 can inhibit tumor growth and metastasis, whereas overexpression of BOLL can reverse this effect. In conclusion, we have reached a preliminary conclusion that upregulation of BOLL by circ_0088300 promotes gastric cancer growth and metastasis by promoting mitochondrial metabolic reprogramming.

Nanodrugs Reprogram Cancer-Associated Fibroblasts and Normalize Tumor Vasculatures for Sequentially Enhancing Photodynamic Therapy of Hepatocellular Carcinoma.

Background: The failure of cancer photodynamic therapy (PDT) is largely ascribed to excessive stroma and defective vasculatures that restrain the photosensitizer permeation and the oxygen perfusion in tumors. Method and Results: In this study, a nanodrug that integrated the cancer-associated fibroblast (CAF) regulation with tumor vessel normalization was tailored to sequentially sensitize PDT. The nanodrug exhibited high targeting towards CAFs and efficiently reversed the activated CAFs into quiescence, thus decreasing collagen deposition in the tumor microenvironment (TME), which overcame the protective physical barrier. Furthermore, the nanodrug regulated vascular endothelial cells and restored the tumor vasculatures, thereby improving vascular permeability. Based on the combined effects of reprogramming the TME, the nanodrug improved tumor accumulation of photosensitizers and alleviated hypoxia in the TME, which facilitated the subsequent PDT. Importantly, the nanodrug regulated the immunosuppressive TME by favoring the infiltration of immunostimulatory cells over immunosuppressive cells, which potentiated the PDT-induced immune response. Conclusion: Our work demonstrates a sequential treatment strategy in which the combination of the CAF regulation and tumor vasculature normalization, followed by PDT, could be a promising modality for sensitizing tumor to PDT.

A predictive model for early death in elderly colorectal cancer patients: a population-based study.

Purpose: The purpose of this study is to determine what variables contribute to the early death of elderly colorectal cancer patients (ECRC) and to generate predictive nomograms for this population. Methods: This retrospective cohort analysis included elderly individuals (≥75 years old) diagnosed with colorectal cancer (CRC) from 2010-2015 in the Surveillance, Epidemiology, and End Result databases (SEER) databases. The external validation was conducted using a sample of the Chinese population obtained from the China-Japan Union Hospital of Jilin University. Logistic regression analyses were used to ascertain variables associated with early death and to develop nomograms. The nomograms were internally and externally validated with the help of the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results: The SEER cohort consisted of 28,111 individuals, while the Chinese cohort contained 315 cases. Logistic regression analyses shown that race, marital status, tumor size, Grade, T stage, N stage, M stage, brain metastasis, liver metastasis, bone metastasis, surgery, chemotherapy, and radiotherapy were independent prognostic factors for all-cause and cancer-specific early death in ECRC patients; The variable of sex was only related to an increased risk of all-cause early death, whereas the factor of insurance status was solely associated with an increased risk of cancer-specific early death. Subsequently, two nomograms were devised to estimate the likelihood of all-cause and cancer-specific early death among individuals with ECRC. The nomograms exhibited robust predictive accuracy for predicting early death of ECRC patients, as evidenced by both internal and external validation. Conclusion: We developed two easy-to-use nomograms to predicting the likelihood of early death in ECRC patients, which would contribute significantly to the improvement of clinical decision-making and the formulation of personalized treatment approaches for this particular population.

Nomogram for predicting occurrence and prognosis of liver metastasis in elderly colorectal cancer patients: a population-based study.

Introduction: This study aimed to explore independent risk and prognostic factors in elderly patients with colorectal cancer liver metastasis (ECRLM) and generate nomograms for predicting the occurrence and overall survival (OS) rates of such patients. Method: Elderly colorectal cancer patients (ECRC) from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. External validation relied on Chinese patients from the China-Japan Union Hospital of Jilin University. Univariate and multivariate logistic regression analyses were employed to identify liver metastasis (LM) risk variables, which were used to create a nomogram to estimate LM probabilities in patients with ECRC. Univariate and multivariable Cox analyses were performed to identify prognostic variables and further derive nomograms that could predict the OS of patients with ERCLM. Differences in lifespan were assessed using the Kaplan-Meier analysis. Finally, the quality of the nomograms was verified using decision curve analysis (DCA), calibration curves, and receiver operating characteristic curves (ROC). Result: In the SEER cohort, 32,330 patients were selected, of those, 3,012 (9.32%) were diagnosed with LM. A total of 188 ECRLM cases from a Chinese medical center were assigned for external validation. LM occurrence can be affected by 13 factors, including age at diagnosis, marital status, race, bone metastases, lung metastases, CEA level, tumor size, Grade, histology, primary site, T stage, N stage and sex. Furthermore, in ECRLM patients, 10 variables, including age at diagnosis, CEA level, tumor size, lung metastasis, bone metastasis, chemotherapy, surgery, N stage, grade, and race, have been shown to be independent prognostic predictors. The results from both internal and external validation revealed a high level of accuracy in predicting outcomes, as well as significant clinical utility, for the two nomograms. Conclusion: We created two nomograms to predict the occurrence and prognosis of LM in patients with ECRC, which would contribute significantly to the improvement in disease detection accuracy and the formulation of personalized cures for that particular demographic.

Complex anal fistula: A case report.

BACKGROUND: Anal fistula is a common benign disease, but the complex type is a difficulty in clinical work. This case featured by its long-term medical course of history and complex clinical appearance. CASE PRESENTATION: Owning to the disease's long-term developing,its appearance is complex and rare. Via medical imaging examinations, we made precise diagnosis as anal fistula, then performed fistulectomy to treat. The patient recovered well in post-operation time. CONCLUSIONS: Complex anal fistula's treatment is the key point while sticking point. Operation is the mainly method to treat presently and enhancing prognosis and reducing complication keep increased. Stem cells are safe and useful for treating anal fistula.

Identification Of Natural Compound Derivative For Inhibition Of XLF And Overcoming Chemoresistance In Colorectal Cancer Cells.

PURPOSE: A previous study has identified that XRCC4-like factor (XLF) is a potential target to overcome resistance to 5-fluorouracil (5-Fu) and oxaliplatin (OXA) in colorectal cancer (CRC). The purpose of this study is to develop potent XLF inhibitors to chemoresistance in CRC. METHODS: Virtual screening was adopted to identify novel XLF-binding compounds by initially testing 6800 molecules in Chemical Entities of Biological Interest library. Hit compounds were further validated by Western blot assay. Cell sensitivity to 5-Fu and OXA was measured using sulforhodamine B assay. The effect of XLF inhibitor on DNA repair efficiency was evaluated by comet assay, fluorescent-based nonhomologous end joining (NHEJ) and homologous recombination (HR) reporter assays. DNA-binding activity of NHEJ key factors was examined by chromatin fractionation assay. RESULTS: We identified G3, a novel and potent XLF inhibitor (IC50 0.47±0.02 µM). G3 induced XLF protein degradation in CRC cells. Significantly, G3 improved cell sensitivity to 5-Fu and OXA in chemoresistant CRC cell lines. Mechanistically, G3 depleted XLF expression, severely compromised NHEJ efficiency by up to 65% and inhibited NHEJ key factor assembly on DNA. G3 also inhibited HR efficiency in a time-dependent manner. CONCLUSION: These results suggest that G3 overcomes 5-Fu and OXA resistance in CRC cells by inhibiting XLF expression. Thus, XLF is a promising target and its inhibitor G3 is a potential candidate for treatment of chemoresistant CRC patients.

O-GlcNAcylation of ITGA5 facilitates the occurrence and development of colorectal cancer.

BACKGROUND/OBJECTIVE: Integrin α5 (ITGA5) as one member of integrins family, plays an important role in promoting cancer cell metastasis and invasion through inducing the communications among different cells or cells with extracellular matrix (ECM). However, the mechanisms underlying ITGA5 in colorectal cancer (CRC) progression need to be explored, especially for its O-GlcNAcylation. To this end, the current study was performed to explore the effects of O-GlcNAcylation on ITGA5 expression, as well as to probe the effects of ITGA5 O-GlcNAcylation on CRC progression. METHODS: The expression profiles of ITGA5, OGT and O-GlcNAc in CRC tissues and cells were detected by immunohistochemistry (IHC), RT-PCR and western blotting. CCK-8, flow cytometry and xenotransplantation assays were used to assess cell growth, apoptosis and tumorigenesis. Immunoprecipitation (IP), in vitro O-GlcNAcylation of ITGA5 and enzymatic labelling of O-GlcNAc assays were used to detect the O-GlcNAcylation of ITGA5 protein. RESULTS: The expression of ITGA5, OGT and O-GlcNAc were all elevated in CRC tissues and cells compared with the normal tissues and cells. Up-regulation of ITGA5 in CRC RKO cells enhanced cell growth and tumorigenesis while decreased cell apoptosis, while down-regulation of ITGA5 in CRC SW620 cells decreased cell growth and tumorigenesis and induced cell apoptosis. Besides, PUGNAc, GlcN or PUGNAc + GlcNAc treatment increased ITGA5 protein expression in RKO and SW620 cells, as well as increased its protein stability via enhancing its O-GlcNAcylation. CONCLUSION: Collectively, the present study makes clear that ITGA5 overexpression accelerates the progression of CRC, which is closely associated to its enhanced O-GlcNAcylation.

MicroRNA (miR)-597-5p Inhibits Colon Cancer Cell Migration and Invasion by Targeting FOS-Like Antigen 2 (FOSL2).

Our previous work had shown that FOS-like antigen 2 (FOSL2) is regulated by miR-143-5p in colorectal cancer (CRC). Given that it has been shown by others that FOSL2 is also a target of miR-597-5p in breast adenocarcinoma, the objective of the current work was to determine whether FOSL2 is regulated by miR-597-5p in CRC and the role of miR-597-5p in CRC. MiR-597-5p expression was determined in RNA obtained from 30 paired samples of colon cancer and tumor adjacent normal tissue, as well as in the LoVo (CRC cell line) and FHC (normal colonic epithelial cells) by quantitative real time polymerase chain reaction (qRT-PCR). MiR-597-5p expression was significantly downregulated in both CRC tissue and LoVo cells. Reporter assays using wild-type and miR-597-5p seed mutant FOSL2 confirmed that FOSL2 is a bona fide target of miR-597-5p. Modulating miR-597-5p expression levels in FHC and LoVo cells using antagomir and mimic, respectively, impacted expression of epithelial and mesenchymal cell markers as well as in vitro migration and invasion, without any effect on cell proliferation, showing that miR-597-5p functions as a suppressor of epithelial to mesenchymal transition. Restoration of FOSL2 expression rescued pro-metastatic functional properties of LoVo cells conforming that effect of miR-597-5p was being mediated by targeting FOSL2. Xenograft assays in athymic nude mice showed that miR-597-5p mimic did not reduce tumor incidence or growth in LoVo cells. However, using a hepatic metastasis model showed that miR-597-5p mimic can significantly prevent hepatic metastatic nodule formation as well as FOSL2 expression in these metastatic nodules. Importantly, FOSL2 mRNA and miR-597-5p expression was found to be inversely correlated in an independent cohort of 21 CRC patients Cumulatively our results show that miR-597-5p functions as a suppressor of metastatic progression in CRC by targeting FOSL2. Replenishment of miR-597-5p can be a potential therapeutic target where its expression along with FOSL2 can serve as potential diagnostic markers in CRC.

Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third commonly diagnosed cancer with a high risk of death. After curative surgery, 40% of patients will have metastases or develop recurrence. Therefore, chemotherapy is significantly responsible as the major therapy method. However, chemoresistance is found in almost all metastatic patients and remains a critical obstacle to curing CRC. MATERIALS AND METHODS: Cell viability is analyzed by sulforhodamine B staining assay. The nonhomologous end joining (NHEJ) repair ability of each cell line was determined by NHEJ reporter assay. mRNA expression levels of NHEJ factors are detected by real-time quantitative polymerase chain reaction. The protein expression levels were observed by western blot assay. RESULTS: Our study found that 5-florouracil (5-Fu) and oxaliplatin (OXA)-resistant HCT116 and LS174T cells showed upregulated efficiency of DNA double-strand repair pathway NHEJ. We then identified that the NHEJ key factor XLF is responsible for the chemoresistance and XLF deficiency sensitizes CRC cells to 5-Fu and OXA significantly. CONCLUSION: Our research first demonstrates that the NHEJ pathway, especially its key factor XLF, significantly contributes to chemoresistance in CRC.

miR­21­5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer.

Pyruvate dehydrogenase A1 (PDHA1) is a component of the pyruvate dehydrogenase enzyme complex, which links glycolysis and the tricarboxylic acid cycle, and is important for cancer metabolism shift. PDHA1 downregulation has been revealed in several types of cancer to enhance glycolysis. However, the role of PDHA1 in gastric cancer remains largely unknown. In the present study, we found that PDHA1 was significantly downregulated in gastric cancer, and associated with poor prognosis. PDHA1 downregulation promoted gastric cancer glycolysis and cancer progression. miR­21­5p directly targeted PDHA1 to suppress PDHA1 expression, and promote glycolysis as well as cell proliferation in gastric cancer. Moreover, miR­21­5p was significantly upregulated in gastric cancer and negatively associated with PDHA1 expression in gastric cancer samples. Our results indicated that miR­21­5p targeted PDHA1 to regulate a metabolic switch and cancer progression in gastric cancer, and reveal the potential role of the miR­21­5p/PDHA1 axis in gastric cancer treatment.

Fos-like antigen 2 (FOSL2) promotes metastasis in colon cancer.

Among different cancers, incidence and mortality of colorectal cancer (CRC) is one of the highest. KRAS mutation is one of the underlying features in the pathogenesis of CRC with CRC tumors harboring mutant KRAS exhibiting a more aggressive behavior compared to CRC tumors with wild type KRAS. We had earlier shown that the microRNA-143 (miR-143) replenishment not only chemosensitizers CRC cell line with mutant KRAS instead of wild-type KRAS gene, to paclitaxel-mediated cytotoxicity, but also inhibits cell migration and invasion ability. Hence, the study aimed to determine how miR-143 replenishment is inhibiting pre-metastatic behavior in CRC cells with mutant KRAS. Top ten mRNA targets of miR-143 as predicted by TargetScan were evaluated by qRT-PCR in LoVo cells which were performed mock transfection or miR-143 mimic transfection. Evaluation of the changes in cognate mRNA target(s) was done in 30 paired CRC tissue and tumor adjacent normal tissue specimens and in LoVo cells by western blot. Effect of the mRNA target on pro-metastatic behavior was assayed by gain- and loss-of-function studies using a combination of western blotting and in vitro cell proliferation and transwell migration/invasion assay in LoVo cells and in the normal colonic epithelium cell line FHC. In vivo effect of the cognate mRNA target on CRC metastasis was assayed by xenograft assay. Of the 10 predicted mRNA targets, FOSL2 (P < 0.05) and IGFBP5 (P > 0.05) was down regulated in LoVo cells transfected with the miR-143 mimic. FOSL2 mRNA levels were significantly downregulated in CRC tissue specimens compared with adjacent normal tissue (P < 0.05). Immunoblot analysis showed that FOSL2, but not IGFBP5, protein expression is down regulated in LoVo cells after the miR-143 mimic transfection. FOSL2 overexpression in the normal colonic epithelial cell line FHC or siRNA-mediated silencing in LoVo cells induced and repressed, respectively, pro-mesenchymal cell features. Whereas manipulation of FOSL2 expression did not have any effect on cell proliferation rates, silencing its expression inhibited cell migration and invasion ability in vitro. In addition, silencing of FOSL2 expression in the LoVo cells can significantly inhibited invasion of hepatic, while no effect was found for tumorigenic potential. Our results suggest that FOSL2 is a critical regulator of CRC metastasis and might be an important marker for prognostic in CRC patients.

[Comparative study of 3D and 2D laparoscopic surgery for gastrointestinal tumors].

OBJECTIVE: To evaluate the technical advantages of 3D laparoscopic and 2D laparoscopic surgery for gastrointestinal tumors. METHODS: Clinical data of gastrointestinal cancer patients undergoing 3D laparoscopic or 2D laparoscopic surgery from January 2015 to January 2017 in our department were retrospectively analyzed These patients included 93 gastric cancer cases undergoing laparoscopic radical resection (total gastrectomy, 48 cases in 3D group, 45 cases in 2D group), 45 rectal cancer cases undergoing radical resection combined with lateral lymph node dissection (27 cases in 3D group, 18 cases in 2D group) and 76 right colon cancer cases undergoing radical resection (37 cases in 3D group, 39 cases in 2D group). The enrolled criteria of cases were 18-80 years old and diagnosed as advanced gastric or colorectal cancer by pathological examination. Patients with preoperative distant metastasis, severe heart or lung diseases who were not suitable for laparoscopic surgery, combined organ resection and conversion to open surgery were excluded. The choice of surgical procedure was determined by the discussion between patients and surgeon. Operations were performed by the same surgical team. Total operation time, complex operation time (deep lymph node dissection time, endoscopic intestinal anastomosis time), number of harvested lymph node, number of times in wrong grasp (accurate grasp for the same site needs to position for two times or more) and intraoperative bleeding were compared between 3D group and 2D group. RESULTS: There were no significant differences in baseline data between 3D group and 2D group. All the patients completed laparoscopic radical operation successfully without conversion to open surgery. In patients with gastric cancer, compared with 2D group, the total operation time was shorter [(185±25) min vs. (190±27) min, P<0.05]; dissection time of No.10 and 11d lymph node [(40±8) min vs. (55±12)min, P<0.05], and No.7, 8, 9 and 12 lymph node [(30±6) min vs. (41±9) min, P<0.05] was shorter; the number of times in wrong grasp (5±2 vs. 11±2, P<0.05) was less in 3D group. In patients with rectal cancer, compared with group 2D, 3D group had shorter time of lateral lymph node dissection [(27±6) min vs. (35±9) min, P<0.05] and laparoscopic anastomosis [(45±7) min vs. (58±11) min, P<0.05]; less number of times in wrong grasp (4±2 vs. 13±2, P<0.05]. In patients with right colon cancer, 3D group had shorter laparoscopic anastomosis time [(38±7) min vs. (44±5) min, P<0.05] and less number of times in wrong grasp (5±1 vs. 13±3, P<0.05] as compared to 2D group. CONCLUSION: 3D laparoscopic surgery for gastrointestinal tumors, compared with 2D laparoscopic technology has significant advantages, which can improve the spatial location and depth of operation, decrease the difficulty of fine operation, and shorten the operation time.

Expression and clinical significance of Beclin-1 in gastric cancer tissues of various clinical stages.

Autophagy is a common phenomenon in cancer metabolism. However the mechanism and guiding significance of autophagy in the development of gastric cancer has remained to be elucidated. In the present study, 75 gastric cancer tissue specimens were collected at The China Japan Union Hospital of Jilin University (Changchun, China). Of these samples, 16 cases were stage 1, 40 stage 2 and 19 stage 3. Polymerase chain reaction and western blotting were used to detect the messenger RNA and protein expression of Beclin-1, a significant protein associated with cellular autophagy. It was found that expression of Beclin-1 in cancer tissues from stages 1 and 2 was higher, while in stage 3 cases levels were significantly lower than that of adjacent normal tissues. In addition, the infiltration of inflammatory cytokines was also increased in stage 1 and 2 cases. In vitro studies revealed that following stimulation with interferon-γ (IFN-γ), autophagy-associated proteins Beclin-1 and microtubule-associated protein light chain 3 were activated. Furthermore, activation of autophagy inhibited xenograft growth in nude mice. The results of these in vivo and in vitro experiments indicated that in gastric cancer tissues, autophagy was downregulated following the development of cancer tissue and that inflammation may be a significant factor in this process. IFN-γ may be involved in the mediation of this process and thus present a novel target for the treatment of gastric cancer.

MicroRNA-143 replenishment re-sensitizes colorectal cancer cells harboring mutant, but not wild-type, KRAS to paclitaxel treatment.

Colorectal cancer (CRC) global incidence is one of the highest among cancers. The KRAS gene has been shown as a robust biomarker for poor prognosis and drug resistance. MicroRNA-143 (miR-143) and let-7 are families of tumor suppressor microRNAs that are often downregulated in CRC, especially with coexistent KRAS mutations. In order to evaluate if miR-143 and/or let-7b replenishment would re-sensitize CRC cells to paclitaxel treatment, we investigated in effect of miR-143 and let-7b replenishments on sensitivity to paclitaxel treatment in KRAS mutant LoVo and wild-type SW48 CRC cell lines. Our results showed that miR-143, but not let-7b, increased sensitization of KRAS mutant tumor cells to paclitaxel. Furthermore, transfection of miR-143, but not let-7b, mimic negatively regulated the expression of mutant but not wild-type KRAS. Combination of miR-143 mimic and paclitaxel induced the onset of apoptosis, and reverted in vitro metastatic properties (migration and invasion) in KRAS mutant tumor cells. MiR-143 thus can be used as a chemosensitizer for the treatment of KRAS mutant tumors and warrants further investigations in in vitro and pre-clinical in vivo models.

MiR-27a promotes hepatocellular carcinoma cell proliferation through suppression of its target gene peroxisome proliferator-activated receptor γ.

BACKGROUND: MicroRNAs (miRNAs) function as essential posttranscriptional modulators of gene expression, and are involved in a wide range of physiologic and pathologic states, including cancer. Numerous miRNAs are deregulated in hepatocellular carcinoma (HCC). This study aimed to investigate the role of miR-27a in the development of HCC. METHODS: The expression of MiR-27a was measured by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to examine changes in the viability of HepG2, Bel-7402, Bel-7404 hepatoma cell lines associated with up-regulation or down-regulation of miR-27a. A dual-luciferase activity assay was used to verify a target gene of miR-27a. Immunohistochemistry, qRT-PCR, Western blotting analysis, and cell cycle and apoptosis flow cytometric assays were used to elucidate the mechanism by which miR-27a modulates liver cancer cell proliferation. RESULTS: The expression of miR-27a was significantly increased in HCC tissues and HepG2, Bel-7402, Bel-7404 hepatoma cell lines (P < 0.05). We also found that the down-regulation of miR-27a in HepG2 cells dramatically inhibited proliferation, blocked the G1 to S cell cycle transition and induced apoptosis (P < 0.05). In addition, miR-27a directly targeted the 3'- untranslated region of peroxisome proliferator-activated receptor γ (PPAR-γ), and ectopic miR-27a expression suppressed PPAR-γ expression on the mRNA and protein levels. The rosiglitazone-induced overexpression of PPAR-γ attenuated the effect of miR-27a in HCC cells. CONCLUSIONS: Our findings suggested that miRNA-27a promoted HCC cell proliferation by regulating PPAR-γ expression. MiR-27a may provide a potential therapeutic strategy for HCC treatment.

Expression and clinical significance of microRNA-376a in colorectal cancer.

The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptase- polymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical follow- up information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.