Prognosis significance and potential association between ALDOA and AKT expression in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract and a leading cause of cancer-related death worldwide. Since many CRC patients are diagnosed already in the advanced stage, and traditional chemoradiotherapy is prone to drug resistance, it is important to find new therapeutic targets. In this study, the expression levels of ALDOA and p-AKT were detected in cancer tissues and paired normal tissues, and it was found that they were significantly increased in CRC tissues, and their high expression indicated poor prognosis. Moreover, a positive correlation between the expression of ALDOA and p-AKT was found in CRC tissues and paired normal tissues. In addition, the Kaplan-Meier analysis revealed that the group with both negative of ALDOA/p-AKT expression had longer five-year survival rates compared with the other group. Besides, the group with both high expression of ALDOA/p-AKT had a worse prognosis compared with the other group. Based on the expression of ALDOA and p-AKT in tumor tissues, we can effectively distinguish tumor tissues from normal tissues through cluster analysis. Furthermore, we constructed nomograms to predict 3-year and 5-year overall survival, showing that the expression of ALDOA/p-AKT plays a crucial role in predicting the prognosis of CRC patients. Therefore, ALDOA/p-AKT may act as a crucial role in CRC, which may provide new horizons for targeted therapies for CRC.

Retroperitoneal totally endoscopic prosthetic repair of lumbar hernia.

Lumbar hernia is a rare lateral abdominal wall hernia. Various surgical repair strategies have been recorded, but there is currently no unified standard. A Chinese surgeon recently revealed a novel technique for treating primary lumbar hernia called retroperitoneal totally endoscopic prosthetic repair (R-TEP). We have made a further exploration of this method and successfully used it in the treatment of secondary lumbar hernia. We successfully performed R-TEP on three patients with lumbar hernias. All patients were female with an average age of 64 years (51-71 years). Two patients each had a primary upper lumbar hernia, while one patient had a secondary lumbar hernia. With a mean operative time of 77 min (60-105 min), all operations were performed successfully. The average visual analogue scale (VAS) was 1.3 points (1-2 points) on the second day following surgery. The mean postoperative hospital stay was 2.3 days (2-3 days). No postoperative complications occurred. During a mean follow-up period of 19 months (10-24 months), there was no recurrence of the hernia, chronic pain or mesh infection. Therefore, R-TEP is safe and effective for both primary and secondary lumbar hernia. Anti-adhesive coated meshes are not required, making this a cost-effective procedure that is worthy of recommendation.

Aberrant expression of AKR1B1 indicates poor prognosis and promotes gastric cancer progression by regulating the AKT-mTOR pathway.

Gastric cancer (GC) is a common malignant tumor in the digestive tract and a major cause of global cancer death. Due to the limited access to early screening, many patients are diagnosed with advanced GC. Therefore, postoperative radiotherapy and chemotherapy possess limited efficacy in treating GC. AKR1B1 has been associated with tumorigenesis and metastasis across various tumors, becoming a potential therapeutic target for GC. However, its role and mechanism in GC remain unclear. In this study, AKR1B1 was elevated in GC tissue, depicting a poor prognosis. AKR1B1 is closely related to age, vascular and neural invasion, lymph node metastasis, and the TNM stage of GC. The developed survival prediction model suggested that AKR1B1 expression level is crucial in the prognosis of GC patients. Moreover, the expression level of AKR1B1 in GC tissues is closely associated with the AKT-mTOR pathway. In vitro and in vivo assays functional assays helped determine the oncogenic role of AKR1B1. Additionally, the knockdown of AKR1B1 expression level in GC cell lines could effectively suppress the AKT-mTOR pathway and inhibit the proliferation and migration of tumor cells. In conclusion, this study provides a theoretical basis to establish the potential association and regulatory mechanism of AKR1B1 while offering a new strategy for GC-targeted therapy.

Overexpression of TYRO3 indicates poor prognosis and induces gastric cancer progression via AKT-mTOR pathway.

Gastric cancer (GC) is among of the leading causes of cancer mortality worldwide. This is because many patients are diagnosed with advanced GC and postoperative radiotherapy and chemotherapy have also exhibited limited effects on GC. TYRO3 has been considered carcinogenic and a potential therapeutic target for GC. However, TYRO3 function and mechanism in GC remains elusive. The study results indicated that TYRO3 was aberrantly elevated in GC tissues and predicted poor prognosis. TYRO3 is closely associated with clinicopathological indicators in GC tissues such as lymph node metastasis, venous invasion, neural invasion, and the tumor-node-metastasis stage. In addition, TYRO3 expression levels are closely related to the AKT-mTOR pathway in GC tissues. Moreover, the oncogenic role of TYRO3 was determined through in vitro and in vivo functional assays, and knockdown of the TYRO3 expression level in GC cell lines can effectively suppress the AKT-mTOR pathway and inhibit tumor cell proliferation and migration. In conclusion, this study provides a theoretical basis for establishing the potential association and regulatory mechanism between TYRO3 and AKT-mTOR and offers a new strategy for GC-targeted therapy.

Prognosis value and positive association of Rab1A/IL4Rα aberrant expression in gastric cancer.

Gastric cancer (GC) is the most common gastrointestinal cancer and the leading cause of worldwide cancer-associated mortality. Several GC patients are diagnosed at the advanced stage with an unsatisfactory 5-year survival rate. Rab1A was significantly associated with IL4Rα expression in non-small cell lung cancer. However, their potential correlation in expression and prognosis remains largely unknown in GC. In this study, Rab1A/IL-4Rα was significantly increased in GC than in para-cancerous tissues, and Rab1A/IL-4Rα overexpression caused poor prognosis among GC patients. Rab1A expression was significantly correlated with IL-4Rα expression in GC tissues, as determined by IHC analysis. In addition, the mRNA expression of Rab1A was closely linked with the IL-4Rα mRNA expression in GC tissue expressed by qPCR. Furthermore, the Kaplan-Meier analysis demonstrated that the group with negative Rab1A and IL-4Rα expression had longer 5-year survival rates than the other group. Besides, the group with positive Rab1A and IL-4Rα expression had a worse prognosis than the other group. Finally, nomograms revealed the overall 3 and 5-year survival determined crucial roles of Rab1A/IL-4Rα expression in predicting the prognosis of GC patients. Therefore, Rab1A/IL-4Rα is vital in GC, providing a novel perspective on targeted GC therapy.

Knockdown of LINC01279 Suppresses Gastric Cancer Proliferation and Migration by Inhibiting PI3K/Akt/mTOR Signaling Pathway.

Objective: To explore the functional and molecular mechanism of long noncoding RNA LINC01279 in gastric cancer (GC). Methods: The LINC01279 expression in GC and tissues of para-carcinoma was detected by qPCR (real-time fluorescent quantitative PCR), and the association between the LINC01279 expression and clinicopathological features of patients with GC was investigated. The colony formation, CCK-8, transwell assays, and cell cycle detection kit were used for detection of the effect of LINC01279 on GC cell proliferation, cell cycle, colony formation, and invasion. The effect of LINC01279 on PI3K/AKT/mTOR in the GC signaling pathway was identified by the Western blotting technique. The effect of LINC01279 on GC cell proliferation in vivo was evaluated by subcutaneous xenograft tumors in the nude mice. Results: The results of qPCR displayed the expression of LINC01279 was higher in tissues of GC patients. Furthermore, the tumor size, TNM stage, and metastasis of lymph nodes were also closely related to LINC01279 expression. The experiments on cell function showed that the LINC01279 knockdown significantly inhibited the colony formation, invasion, and proliferation of GC cells and induced the cell cycle arrest in G0 and G1 phases. The Western blotting technique also showed that LINC01279 knockdown significantly inhibited the phosphorylation of PI3K, Akt, and mTOR in GC cells. Furthermore, in vivo experiments displayed that the LINC01279 knockdown significantly inhibited the GC growth. Conclusion: Knockdown of LINC01279 plays a significant role in inhibiting the PI3K/AKT/mTOR signaling pathway which affects the GC invasion and proliferation. The LINC01279 expression can be utilized as a biomarker for the prediction of the GC prognosis.

Absent in melanoma 2 suppresses gastric cancer cell proliferation and migration via inactivation of AKT signaling pathway.

Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and poses a great threat to public health. Absent in melanoma 2 (AIM2), a member of the pyrin-HIN family proteins, plays various roles across different types of cancers. However, the possible role of AIM2 in GC, as well as the underling mechanisms, are equivocal and need to be further explored. Herein, we identified that AIM2 expression was significantly down-regulated in GC tissues. Furthermore, loss of AIM2 was significantly associated with tumor size, lymph node metastasis (LNM) and tumor, node, metastases (TNM) staging, as well as poor prognosis in GC patients. Knockdown of AIM2 in GC cells significantly promoted cellular proliferation and migration, whereas AIM2 overexpression did the opposite. Mechanistically, we discovered that AIM2 regulates the AKT signaling pathway. In fact, the enhanced proliferation and migration ability induced by AIM2 knockdown was partially impaired in cells treated with the AKT inhibitor. Overall, our findings suggests that AIM2 is an independent prognostic marker and highlights a new entry point for targeting the AIM2/AKT signaling axis for GC treatment.

AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1.

Colorectal cancer (CRC) is a common malignant tumor and is one of the leading causes of cancer-related deaths worldwide. Absent in melanoma 2 (AIM2), as a member of the pyrin-HIN family proteins, plays contentious roles in different types of cancers. In the present work, we provide evidence that AIM2 was commonly downregulated in human CRC and loss of AIM2 significantly correlated with tumor size, depth of invasion, lymph node metastasis (LNM) and TNM (Tumor, Node, Metastases) stage in patients suffering from CRC. AIM2 knockdown promoted CRC cell proliferation, migration and epithelial-mesenchymal transition (EMT) progress, whereas AIM2 overexpression did the opposite. AIM2 inhibited glioma-associated oncogene-1 (Gli1) expression through Smoothened homolog (SMO)-independent pathway and regulated CRC cell proliferation and migration in a Gli1-dependent manner. Moreover, AIM2 could modulate Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway and the increased Gli1 expression and EMT progress induced by AIM2 depletion was reversed after incubation with AKT inhibitor Ly294002 in CRC cells. In conclusion, our results define AIM2 as a novel regulator of Gli1 in CRC cell growth and metastasis, and suggest that the AIM2/AKT/mTOR/Gli1 signaling axis may serve as a potential target for treatment of CRC.

Clinical value and potential association of Rab1A and FoxM1 aberrant expression in colorectal cancer.

Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. Our recent study indicated that Rab1A expression was closely related to GLI1 expression. A previous study shows that aberrant overexpression of GLI1 promotes colorectal cancer metastasis via FoxM1 overexpression. However, the potential correlation between Rab1A and FoxM1 in CRC remains elusive. Immunohistochemistry was performed to investigate the association of the expression of Rab1A and FoxM1 and to determine the prognosis in 135 CRC tissue and adjacent normal tissues. Using Oncomine datasets, we found that Rab1A and FoxM1 mRNA were obviously upregulated in CRC tissues compared to normal tissues. Additionally, the expression of Rab1A and FoxM1 was significantly higher in CRC tissues than that in normal tissues. Rab1A expression was positively correlated with FoxM1 expression in CRC, especially in TNM stage III. In addition, Rab1A and FoxM1 overexpression was found to be significantly correlated with poor prognosis in CRC patients. Besides, both high expression of Rab1A and FoxM1 led to a worse prognosis than anyone low group, and both low expression of Rab1A and FoxM1 had a better prognosis than the anyone low group. Therefore, Rab1A and FoxM1 play crucial roles and could be used as clinical biomarkers in CRC.

Yes-Associated Protein Contributes to Cell Proliferation and Migration of Gastric Cancer via Activation of Gli1.

OBJECTIVE: In the present study, we aimed to explore the potential oncogenic property and the internal mechanism of yes-associated protein (YAP) in gastric cancer (GC). MATERIALS AND METHODS: YAP protein levels were evaluated in human GC tissues and paired normal tissues using immunohistochemistry (IHC). The role of YAP in regulating GC cell proliferation and migration was verified by genetic manipulation in vitro. Western blot analysis was used to determine the molecular signaling to explain the mechanism of the observed YAP effects in GC. RESULTS: Nuclear YAP protein expression was upregulated in GC tissues, and high nuclear YAP level was significantly correlated with lymph node metastasis (LNM) and tumor node metastasis (TNM) stage in patients suffered from GC. YAP knockdown inhibited GC cell proliferation, migration and epithelial-mesenchymal transition (EMT) progress in vitro, whereas YAP elevation did the opposite. YAP regulated glioma-associated oncogene-1 (Gli1) expression independent of smoothened homolog (SMO). YAP modulated protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway in GC cells. CONCLUSION: YAP enhanced GC cell proliferation and migration potentially via its regulation of Gli1 expression through the non-classical Hedgehog pathway, indicating suppression of YAP/Gli1 signaling axis may highlight a new entry point for combination therapy of GC.

Pooled analysis of prognostic value and clinical significance of Rab1A expression in human solid tumors.

BACKGROUND: This study aims to assess the relationship between Rab1A expression and clinicopathological parameters and prognosis of patients with human solid cancer by summarizing the studies included. METHODS: PubMed, EMBASE, The Cochrane Library, and other sources were searched for relative studies. The risk ratios (RRs) and confidence interval (CI) were used to assess association between Rab1A expression and clinical parameters and prognosis in solid cancer patients. RESULTS: Eight studies were included in the final analysis with 800 patients. The results revealed that expression of Rab1A was significantly related with differentiation (RR = 0.883, 95%CI = 0.782-0.997, P = .044), lymph node metastasis (RR = 0.835, 95%CI = 0.753-0.926, P = .001), tumor-lymph node-metastasis (TNM) stage (RR = 1.190, 95%CI = 1.071-1.322, P < .001) and tumor size (RR = 0.818, 95%CI = 0.730-0.915, P < .001). What is more, no significant difference was seen in 1-year survival between high and low expression of Rab1A in multiple malignancies (RR = 0.855, 95%CI = 0.697-1.050, P = .136). However, increased Rab1A revealed poorer prognosis with 2-year survival (RR = 0.760, 95%CI = 0.701-0.824, P < .001), 3-year survival (RR = 0.669, 95%CI = 0.604-0.742, P < .001), 4-year survival (RR = 0.622, 95%CI = 0.554-0.698, P < .001) and 5-year survival (RR = 0.525, 95%CI = 0.458-0.698, P < .001). Expression of Rab1A was increased obviously in solid cancer tissues compared with the adjacent normal tissue (RR = 4.78, 95%CI 4.05-5.63, P = .015). CONCLUSION: This study revealed Rab1A expression links closely with tumor size, differentiation, lymph node metastasis, TNM stage and poor prognosis of human solid cancer patients. It may act as a biomarker of prognosis and a novel therapeutic target in solid cancer.

Expression analysis and implication of Rab1A in gastrointestinal relevant tumor.

Gastrointestinal cancers have become increasingly prevalent worldwide. Previous studies have reported an oncogenic function of Rab1A in colorectal cancer and hepatocellular carcinomas via the mTOR pathway. However, the exact role of Rab1A in gastrointestinal cancers remains elusive. We detected significantly higher expression of Rab1A in the gastrointestinal tumor tissues compared to that in other cancer types following an in silico analysis of TGCA and GTEX databases. Furthermore, Rab1A was overexpressed in the gastrointestinal tumor tissues compared to the para-tumor tissues. Although Rab1A expression levels were not associated with the tumor-lymph node-metastasis (TNM) stage, Rab1A overexpression in the tumor tissues of a gastric cancer (GC) cohort was strongly correlated with poor prognosis in the patients. In addition, Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of GC cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. Taken together, Rab1A regulates the PI3K-AKT-mTORC1 pathway through the mTORC1 complex consisting of mTORC1, Rheb and Rab1A, and is a promising therapeutic target in GC.

Prognosis, Significance and Positive Correlation of Rab1A and p-S6K/Gli1 Expression in Gastric Cancer.

BACKGROUND: Gastric Cancer (GC) is a frequently common malignancy. Recent studies have reported Rab1A as an activator of mTORC1, and the mTOR1 pathway is involved in regulating Gli1 expression in several cancers. Only a few studies have been performed to explore the relationship between Rab1A and p-S6K/Gli1in GC. METHODS: Immunohistochemistry (IHC) was performed to explore the association of Rab1A/p-S6K/Gli1 expression and prognosis in 117 GC tissue samples and adjacent normal tissues. RESULTS: Our results indicated that Rab1A/p-S6K/Gli1 was significantly overexpressed in GC tissues. High expression of Rab1A was closely related to the tumor size and the depth of tumor invasion. In addition, Rab1A expression was closely related with p-S6K/Gli1 expression in GC, and high level of Rab1A/p-S6K/Gli1 caused worse prognosis of GC patients. The univariate and multivariate analysis indicated that the expression of Rab1A was an independent prognostic factor. Moreover, both high Rab1A and p-S6K expression led to a worse prognosis when compared to a single positive expression as well as both high Rab1A/Gli1 expression also led to a worse prognosis than the single positive expression of Rab1A/Gli1. Strikingly, the overexpression of p-S6K also led to a worse prognosis in Rab1A positive patients, as did Gli1. CONCLUSION: Our results indicate that Rab1A/mTOR/S6K/Gli1 axis played a crucial role in GC, which may provide a novel field on targeted therapy of GC, especially for mTORC1-targeted therapy-resistant cancers.

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer.

Colorectal carcinoma (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer­related deaths in the US. Recently, Rab1A has been reported to be an activator of mTORC1 and p­S6K1, which is downstream of mTORC1. However, the association between Rab1A and p­S6K1 in CRC remains elusive. In the present study, we first demonstrated that Rab1A was overexpressed in CRC tissues and Rab1A overexpression was positively related to lymph node invasion, degree of differentiation, venous invasion and tumor­node­metastasis (TNM) stage. In both TNM stage I­II and III­IV patients, Rab1A­positive patients had a shorter survival time than Rab1A­negative patients. Furthermore, in univariate and multivariate analyses, only Rab1A expression was verified as an independent prognostic factor for survival in CRC patients. The level of p­S6K1 was markedly high in CRC tissues and Rab1A expression level had a positive association with p­S6K1 level. In addition, high levels of both Rab1A and p­S6K1 were associated with a poorer prognosis compared with low expression of either Rab1A or p­S6K1 level. Moreover, high levels of both Rab1A and p­S6K1 were associated with a poorer prognosis than patients with high levels of either Rab1A or p­S6K1 alone. Finally, knockdown of Rab1A expression inhibited migration and proliferation of SW480 and HCT116 cell lines by targeting regulation of p­S6K1. Thus, our findings indicate that Rab1A plays an important role in CRC and may provide a therapeutic target for CRC, particularly for mTORC1­targeted therapy­resistant cancers.

ENO1 Acts as a Prognostic Biomarker Candidate and Promotes Tumor Growth and Migration Ability Through the Regulation of Rab1A in Colorectal Cancer.

BACKGROUND: Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. The glycolytic enzyme α-enolase (ENO1) is overexpressed in multiple cancers and is involved in tumor cell proliferation and metastasis. However, its clinical significance, biological role, and underlying molecular mechanisms in CRC are still unclear. The aim of the present study was to investigate the potential role of ENO1 in the initiation and development of CRC. PATIENTS AND METHODS: The in situ expression of ENO1 in CRC and adjacent normal tissues was examined by immunohistochemistry. The effects of ENO1 on the in vitro proliferation and migration of CRC cell lines were investigated by MTT, colony formation, and Transwell assays. Finally, the in vivo tumorigenic capacity of ENO1 was assessed in a mouse model. RESULTS: ENO1 was overexpressed in CRC tissues and significantly correlated with the clinicopathological parameters. Furthermore, Rab1A was also overexpressed in CRC tissues and was positively correlated to that of ENO1. The high expression levels of both ENO1 and Rab1A led to significantly worse prognosis of CRC patients compared to either alone. Furthermore, knockdown of ENO1 significantly inhibited CRC cells proliferation and migration in vitro and reduced xenograft growth in vivo via the concomitant downregulation of Rab1A. CONCLUSION: The ENO1/Rab1A signaling axis is involved in CRC progression and is a potential biomarker for the treatment of CRC.