ZNF521/EBF1 axis regulates AKR1B1 to promote the proliferation, migration, and invasion of gastric cancer cells.

Although the incidence and death rates of gastric cancer (GC) are decreasing, approximately one million new cases and 800,000 GC-related deaths were reported worldwide in 2018. Currently, the oncogenesis of GC remains unclear, and the demand for novel treatment options are unmet. Here, we explored the role of aldo-keto reductase family 1 member B (AKR1B1) in the progression of GC. The proliferation, migration, and invasion of GC cells were evaluated by CCK-8 assay, wound healing assay, and transwell assay, respectively. The interaction between EBF transcription factor 1 (EBF1) and the promoter region of AKR1B1 was determined by luciferase reporter assay and chromatin immunoprecipitation (ChIP). Gene expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting assay. The expression of AKR1B1 was elevated in GC cells, resulting in increased cell proliferation, migration, and invasion. Meanwhile, EBF1 was a negative regulator of AKR1B1; its overexpression suppressed AKR1B1 expression and GC progression. Furthermore, knockdown of ZNF521 induced EBF1 expression, thus suppressing AKR1B1 expression and resulting in attenuated GC growth and invasiveness. Notably, knockdown of ZNF521 attenuated GC progression and was rescued by overexpression of AKR1B1. Our current study revealed a novel ZNF521/EBF1/AKR1B1 axis in GC and elaborated its important role in promoting GC progression, providing potential therapeutic targets for anti-GC treatments.

LncRNA DLEU1 facilitates the progression of oral squamous cell carcinoma by miR-126-5p/GAB1 axis.

Oral squamous cell carcinoma (OSCC) is one of the most frequent malignancies found in head and neck cancers. Dysregulation of lncRNAs has been proposed to be related to the development of OSCC. Here, we investigated the function and probable mechanisms of lncRNA DLEU1 in OSCC. OSCC cell lines and human oral keratinocytes (HOKs) were cultured, while SCC-25 and CAL-27 cells were transfected with the corresponding plasmids. Reverse transcription quantitative PCR (RT-qPCR) and western blot were carried out to measure the RNA and protein levels. Cell proliferation, migration and invasion were evaluated using MTT assays, wound healing and Transwell assays. The StarBase database predicted the interactions between DLEU1 and miR-126-5p, as well as miR-126-5p and GAB1, which were further validated using a dual-luciferase reporter assay. Our results indicated that DLEU1 and GAB1 were upregulated, while miR-126-5p was downregulated in OSCC cells. Silencing DLEU1 reduced OSCC cell proliferation, migration, and invasion, while DLEU1 overexpression had the opposite effects. DLEU1 mediated biological effects in OSCC through binding to miR-126-5p, which directly targeted GAB1. miR-126-5p knockdown rescued the inhibitory function of DLEU1 depletion on proliferation, migration and invasion. Meanwhile, the miR-126-5p mimic exerted suppressive functions in the progression of OSCC, which were neutralized after GAB1 overexpression. In summary, lncRNA DLEU1 targets the miR-126-5p/GAB1 axis to aggravate OSCC progression, providing a novel target for treating OSCC.

circBANP promotes colorectal cancer growth and metastasis via sponging let-7d-5p to modulate HMGA1/Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is one of the most common and deadly cancers, and the incidence of CRC is on the rise. Due to the lack of early diagnosis method and high metastasis of the disease, the prognosis of CRC remains very poor. Exploring the underlying molecular mechanisms of CRC is very necessary for effective therapy. In this study, we investigated the function of circBANP in CRC. The results showed that circBANP was elevated in both CRC tissues and cells and its level positively correlated with the stage of CRC. Knockdown of circBANP greatly suppressed the epithelial-mesenchymal transition (EMT) process and CRC cell proliferation, migration, and invasion. In addition, knockdown of circBANP inhibited CRC tumor growth and metastasis in vivo. Further, circBANP directly bound to let-7d-5p and regulated CRC development via acting as a let-7d-5p sponge. Let-7d-5p directly targeted HMGA1 and thus circBANP/let-7d-5p regulated Wnt/ß-catenin signaling via HMGA1. Collectively, circBANP promotes CRC development and metastasis via acting as a let-7d-5p sponge to regulate HMGA1/Wnt/ß-catenin signaling, providing a potential biomarker and therapeutic target for the management of CRC.

Clinical efficacy of DC-CIK combined with sorafenib in the treatment of advanced hepatocellular carcinoma.

PURPOSE: To explore the therapeutic efficacy and safety of the combination treatment of dendritic cells and cytokine-induced killers (DC-CIK) and sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients diagnosed with advanced HCC and treated with DC-CIK and/or sorafenib in the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University from January 2015 to January 2016 were retrospectively analyzed. HCC patients were divided into (A): control group (oral administration of sorafenib) and (B): observation group (oral administration of sorafenib combined with DC-CIK). Patients were followed up every 4-8 weeks. Overall survival and adverse events of each patient were recorded. Therapeutic efficacy was evaluated using the modified RECIST criteria. RESULTS: After treatment, ALT and TBIL were remarkably elevated in the control group and decreased in the observation group. No significant change in AFP level was seen in the control group after treatment, whereas it was remarkably decreased in the observation group. The efficacy rate was 16.7% and 51.4% in the control and observation group, respectively. Clinical benefit rate (CBR) was 41.9% and 88.6% in the control group and observation group, respectively. The median survival time of the control and observation group was 13.8 and 18.6 months, respectively. In the observation group there was a significant difference in the survival time between patients with Child-Pugh A and Child-Pugh B, respectively. CONCLUSIONS: DC-CIK combined with sorafenib could improve the tumor response rate and prolong overall survival of advanced HCC without increasing the incidence of adverse events. HCC patients achieve a more stable disease condition and longer overall survival with DC-CIK combined with sorafenib than those with individual sorafenib treatment.

High Rab27A expression indicates favorable prognosis in CRC.

BACKGROUND: Rab27A is a peculiar member in Rab family and has been suggested to play essential roles in the development of human cancers. However, the association between Rab27A expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet. METHODS: One-step quantitative real-time polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 112 CRC cases were executed to evaluate the relationship between Rab27A expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for 112 CRC patients. RESULTS: The results specified that the expression levels of Rab27A mRNA and protein were significantly higher in CRC tissues than that in matched non-cancerous tissues, in both qPCR test (p = 0.029) and IHC analysis (p = 0.020). The IHC data indicated that the Rab27A protein expression in CRC was statistically correlated with lymph node metastasis (p = 0.022) and TNM stage (p = 0.026). Cox multi-factor analysis and Kaplan-Meier method suggested Rab27A protein expression (p = 0.012) and tumor differentiation (p = 0.004) were significantly associated with the overall survival of CRC patients. CONCLUSION: The data indicated the differentiate expression of Rab27A in CRC tissues and matched non-cancerous tissues. Rab27A may be used as a valuable prognostic biomarker for CRC patients.

Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro.

Cell­based therapy is a potential alternative to liver transplantation. The goal of the present study was to examine the in vivo and in vitro hepatic differentiation potential of adipose tissue­derived mesenchymal stem cells (AT­MSCs) and to explore its therapeutic use. AT­MSCs were isolated and cultured with hepatic differentiation medium. Bioactivity assays were used to study the properties of AT­MSCs. The morphology of differentiated AT­MSCs in serum­free hepatic differentiation medium changed into polygonal epithelial cells, while the morphology of AT­MSCs in a similar medium containing 2% fetal bovine serum remained unchanged. The differentiated cells cultured without serum showed hepatocyte­like cell morphology and hepatocyte­specific markers, including albumin (ALB) and α­fetoprotein. The bioactivity assays revealed that hepatocyte­like cells could take up low­density lipoprotein (LDL) and store glycogen. Furthermore, trichostatin A (TSA) enhanced ALB production and LDL uptake by the hepatocyte­like cells, analogous to the functions of human liver cells. ALB was detected in the livers of the CCl4­injured mice one month post­transplantation. This suggested that transplantation of the human AT­MSCs could relieve the impairment of acute CCl4­injured livers in nude mice. This therefore implied that adipose tissue was a source of multipotent stem cells which had the potential to differentiate into mature, transplantable hepatocyte­like cells in vivo and in vitro. In addition, the present study determined that TSA was essential to promoting differentiation of human MSC towards functional hepatocyte­like cells. The relief of liver injury following treatment with AT­MSCs suggested their potential as a novel therapeutic method for liver disorders or injury.

Alpha B-crystallin correlates with poor survival in colorectal cancer.

Alpha B-crystallin (CRYAB) is primarily found as major structural proteins of the ocular lens and is a principal member of the small heat shock protein (HSP) family. So far, CRYAB has been suggested to play critical roles in the development of several kinds of human cancers. However, the association between CRYAB expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet. In the present study, one-step quantitative PCR reverse transcription-polymerase chain reaction (qPCR) analysis of 18 samples of CRC and immunohistochemistry (IHC) analysis with 100 cases of CRC sample in tissue microarrays (TMA) were employed to evaluate the expression of CRYAB in CRC. The results suggested that CRYAB expression in the mRNA and protein levels was significantly higher in CRC tissues than in corresponding non-cancerous tissues (P < 0.05 and P = 0.014, respectively). The expression of CRYAB protein in CRC was significantly associated with distant metastasis (P = 0.040) and overall survival (P = 0.003). Kaplan-Meier method and multivariate survival analysis indicated that high expression of CRYAB (P = 0.040) and distant metastasis (P = 0.005) showed significant correlations with poor prognosis of CRC patients. The data imply that CRYAB expression is correlated with substantial clinical characteristics of CRC, and it may be identified as an unfavorable prognostic factor for CRC.

Elevated expression of CRYAB predicts unfavorable prognosis in non-small cell lung cancer.

Alpha B-crystallin (CRYAB) is one of the principal members of the small heat-shock protein family, and several studies described the CRYAB expression in human cancers. However, the association between CRYAB expression and the clinical features of non-small cell lung cancer (NSCLC) is rarely elucidated. In this present study, one-step quantitative reverse transcription-polymerase chain reaction with 12 fresh-frozen NSCLC samples and Western blotting as well as immunohistochemistry (IHC) analyses in 101 NSCLC cases were conducted to investigate the relationship between CRYAB expression and the clinicopathological attributes of NSCLC. The results showed that CRYAB mRNA and protein expression levels were significantly higher in NSCLC than in matched non-cancerous tissues (p < 0.05). The IHC data indicated that the CRYAB protein expression in NSCLC was significantly correlated with TNM stage (p = 0.043), and overall survival (p = 0.029). Kaplan-Meier method and Cox multifactor analysis suggested that higher CRYAB protein level (p = 0.032) and TNM stage (p = 0.048) were statistically associated with the poor survival of patients with NSCLC. The data suggested that CRYAB may be identified as a novel prognostic marker and targeting CRYAB may provide a promising strategy for NSCLC treatment.

Rab27b is a potential predictor for metastasis and prognosis in colorectal cancer.

Objective. Rab27b is reported to correlate with cancer development and progression. However, the association between Rab27b expression and the clinical characteristics of colorectal cancer (CRC) is barely investigated. Methods. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 113 CRC cases were performed to explore the relationship between Rab27b expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were executed to evaluate the prognosis of CRC. Results. The results demonstrated that the expression levels of Rab27b mRNA and protein were significantly higher in CRC tissues than that in matched noncancerous tissues (P < 0.05). Rab27b protein expression in CRC was statistically correlated with serum CEA level (P = 0.004), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), and TNM stage (P = 0.001). Cox multifactor analysis and Kaplan-Meier method suggested that higher Rab27b protein expression (P = 0.041) and tumor differentiation (P = 0.001) were significantly associated with the overall survival of CRC patients. Conclusions. The data indicated that higher expression of Rab27b was observed in CRC tissues and Rab27b may be identified as a useful predictor of metastasis and prognosis for CRC.