MiR-148a may serve as a novel biomarker for the diagnosis and as a new therapeutic target in gastric cancer.
PTENP1 has been demonstrated to function as a tumor suppressor in several cancer cells. However, its expression and biological roles in gastric cancer (GC) have not yet been investigated. In this study, we demonstrated that PTENP1 was frequently decreased in GC tissues and cell lines, which might be partly associated with DNA hypermethylation, and lower PTENP1 expression was associated with larger tumor size, more advanced stage, deeper invasion depth and lymphatic metastasis. In addition, our data suggested that PTENP1 could regulate GC cell proliferation, apoptosis, migration and invasion in vitro. Furthermore, we demonstrated that PTENP1 could modulate the PTEN protein expression. Taken together, these results suggest that PTENP1 functions as a novel tumor suppressor in GC and its suppressive ability may be involved in the modulation of PTEN.
Introduction: As it is not clear whether growth arrest-specific 5 (GAS5) inhibits gastric cancer (GC) cell proliferation by regulating cell cycle, we analyzed the effect of GAS5 on cell cycle regulation of GC cells and explored the underlying mechanism. Methods: We measured GAS5 levels in GC tissues and corresponding normal tissues, and analyzed the role of GAS5 in regulation of cell proliferation and cell cycle in GC cells using CCK-8 assay and flow cytometry. We also measured the expression of P21 and CDK6 proteins after transfection of AGS and MGC-803 cells with pLJM-GAS5 and GAS5 siRNA, respectively, by western blotting. Results: GAS5 expression was significantly lower in GC tissues relative to normal tissues, and its lower expression was correlated with larger tumor size and a more advanced clinical stage of GC. GAS5 induced growth arrest of GC cells through inhibition of G1-S phase translation. The action of GAS5 may be mediated by upregulation of P21 and suppression of CDK6. Conclusion: These data enhance our understanding of the important role that GAS5 plays in the molecular etiology of GC and suggest a potential of GAS5 as a new therapeutic target for GC treatment.
Gastric cancer is one of the most common malignant diseases and remains the second leading cause of cancer-related mortality worldwide. Although great effort has been made during the past decades to facilitate the early detection and treatment of gastric cancer, the prognosis is not yet satisfactory and the underlying molecular mechanisms of gastric cancer pathogenesis are not fully understood. Meanwhile, non-coding RNAs have been established as key players in regulating various biological and pathological processes, such as cell-cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Furthermore, numerous studies have also revealed a complicated interplay among different species of non-coding RNAs; therefore, the cross-regulation between long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) has begun to emerge. This lncRNA-miRNA cross talk, which has attracted increasing attention in recent years, is involved in a great number of human diseases including gastric cancer. In this review, we summarize the latest research progress of the interactions between lncRNAs and miRNAs, highlighting their influences on the development and progression of gastric cancer to provide novel approaches for cancer diagnosis and treatment.
Tumor metastasis is the most common cause of cancer-related deaths, yet it remains poorly understood. The transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) is involved in the epithelial-to-mesenchymal transition (EMT) and plays a pivotal role in tumor metastasis. However, the underlying mechanisms of the posttranslational modification of ZEB1 remain largely unknown. Herein, we demonstrated that specific inhibition of CDK4/6 was able to block tumor metastasis of breast cancer by destabilizing the ZEB1 protein in vitro and in vivo. Mechanistically, we determined that the deubiquitinase USP51 is a bona fide target of CDK4/6. The phosphorylation and activation of USP51 by CDK4/6 is necessary to deubiquitinate and stabilize ZEB1. Moreover, we found a strong positive correlation between the expression of p-RB (an indicator of CDK4/6 activity), p-USP51 and ZEB1 in metastatic human breast cancer samples. Notably, the high expression of p-RB, p-USP51, and ZEB1 was significantly correlated with a poor clinical outcome. Taken together, our results provide evidence that the CDK4/6-USP51-ZEB1 axis plays a key role in breast cancer metastasis and could be a viable therapeutic target for the treatment of advanced human cancers.
Gastric cancer (GC) remains a major public health issue as the second leading cause of cancer-related death and the fourth most common cancer worldwide. Although much progress has been achieved in recent years, the early diagnosis and treatment for GC are not yet satisfactory; thus, the prognosis remains poor. Therefore, identification of novel molecules for early diagnosis, prognosis, and treatment is urgently needed. Long non-coding RNAs (lncRNAs) are a new class of non-coding RNAs that participate in a variety of biological processes such as cell proliferation, cell cycle, differentiation, and apoptosis, mainly by regulation of gene expression at various levels, including chromatin, splicing, transcriptional, and post-transcriptional levels. Some lncRNAs are upregulated in cancer and possess oncogenic properties, while others exhibit aberrant low expression and act as tumor suppressors. In this review, we overview the functional roles and regulatory mechanisms of lncRNAs in GC and evaluate their diagnostic, prognostic, and therapeutic values.
Tristetraprolin (TTP) is an adenine/uridine (AU)-rich element (ARE)-binding protein that can induce degradation of mRNAs. In this study, we report that TTP suppresses the expression of interleukin-33 (IL-33), a tumor-promoting inflammatory cytokine, and thereby inhibits the progression of gastric cancer (GC). Overexpression of TTP decreased the level of IL-33, whereas knockdown of TTP increased IL-33 levels. We also discovered that TTP inhibited the proliferation, migration, and invasion of GC cell lines through regulation of IL-33. Furthermore, TTP RNA and protein levels were remarkably reduced in GC and inversely correlated with IL-33 level, and they were also closely associated with depth of invasion, lymph node metastasis, advanced TNM stage, as well as survival rate. Taken together, these findings identified TTP as a downregulator of IL-33, and further suggest that TTP can serve as a novel biomarker for the diagnosis of GC and as a potential therapeutic target for GC treatment.
Long non-coding RNAs (lncRNAs) have been widely studied in recent years, and accumulating evidence identified lncRNAs as crucial regulators of various biological processes, including cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. In addition, the fact that lncRNAs interact with the MYC gene family in human carcinomas has been discovered. This review summarizes the latest progress on the investigation of lncRNAs and MYC, particularly focusing on the interplay between lncRNAs and MYC in cancer to reveal the significance of lncRNA-MYC network in regulating initiation, development, and metastasis of tumors. Further research and collection of clinical data would provide a better understanding of lncRNA-MYC network in cancer diagnosis and treatment.
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