A systematic assessment of statistics, risk factors, and underlying features involved in pancreatic cancer

Aier, Imlimaong; Semwal, Rahul; Sharma, Anju; Varadwaj, Pritish Kumar

doi:10.1016/j.canep.2018.12.001

Cited by 103 publications

(90 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, PC has received increasing attention due to its high incidence and extremely poor prognosis [18]. Accumulated studies have shown that lncRNAs play an important role in the initiation and development of cancers, including PC [19].…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA LINC00514 accelerates pancreatic cancer progression by acting as a ceRNA of miR-28-5p to upregulate Rap1b expression

Han

Xiong

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background: Pancreatic cancer (PC) is one of the most aggressive cancers and has an extremely poor prognosis worldwide. Long noncoding RNA (lncRNA) has been reported to be a potential prognostic biomarker in the initiation and prognosis of PC. Nevertheless, the biological functions and the detailed molecular mechanism of LINC00514 in PC remain unclear. Methods: We measured the expression level of LINC00514 in PC tissues and cell lines by quantitative real-time PCR. Gain-and loss-of-function experiments were performed to explore the bioeffects of LINC00514 on PC development both in vitro and in vivo. Subcellular fractionation, luciferase reporter assay, RNA immunoprecipitation assay, pulldown assay and western blotting were performed to investigate the oncogenic molecular mechanisms of LINC00514. Results: In this study, LINC00514 was shown to be upregulated in PC tissues and cell lines. Increased LINC00514 expression was significantly associated with the clinical progression and prognosis of PC patients. In addition, silencing LINC00514 inhibited PC cell proliferation, migration and invasion, while LINC00514 overexpression promoted these processes. Moreover, LINC00514 knockdown remarkably inhibited PC development and metastasis in vivo. Deeper investigations indicated that LINC00514 acted as a sponge for microRNA-28-5p (miR-28-5p) in PC and that Rap1b was a downstream target of miR-28-5p. Furthermore, the positive correlation of LINC00514 and Rap1b and the negative correlation between miR-28-5p and LINC00514 (or Rap1b) were revealed. Based on the rescue assays, Rap1b inhibition partially suppressed the oncogenic effect of LINC00514 overexpression on PC cell proliferation, migration and invasion. Conclusions: This study is the first to characterize the oncogenic function of the long noncoding RNA LINC00514 in pancreatic cancer progression by acting as a competing endogenous RNA (ceRNA) of miR-28-5p to upregulate Rap1b expression. Understanding this molecular mechanism might contribute to further discoveries of better diagnostic and therapeutic options for pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA LINC00514 accelerates pancreatic cancer progression by acting as a ceRNA of miR-28-5p to upregulate Rap1b expression

Han

Xiong

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the world with a low probability of early diagnosis [1] . KRAS, CDKN2A, TP53, and SMAD4 are frequently mutated genes that define the genetic landscape of PDAC.…”

Section: Introductionmentioning

confidence: 99%

“…PDAC is one of the most lethal cancers due to its high metastatic potential and delayed detection [2,3] . The median survival time following diagnosis remains at less than 6 months, with an overall survival rate of less than 4% [1][2][3] . Gemcitabine (GEM) treatment has only increased the median survival of PDAC patients from 3-4 months to 6-7 months [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Safa

2020

JCMT

View full text Add to dashboard Cite

Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). Tumor dissemination is associated with the activation of an epithelial-tomesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell-tocell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger the phenotypic transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs) or cancer-initiating cells in pancreatic tumors. PCSCs may represent sub-populations of tumor cells resistant to therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen as well as the drug transporter ABCG2 grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights a linkage between CSC and EMT. In this review, The current understanding of the PCSCs, signaling pathways regulating these cells, PDAC heterogeneity, EMT mechanism, and links between EMT and metastasis in PCSCs

show abstract

“…According to GLOBOCAN [1], the incidence rate for this cancer is highest in Europe and North America, with equal incidences in both male and female population. This makes pancreatic cancer the fourth leading cause of cancerrelated death in the world [2,3]. Besides the lack of early detection and diagnosis, a major obstacle that lies in the pathway of PDAC treatment is the drug-resistant phenotype, which develops overtime [4].…”

Section: Introductionmentioning

confidence: 99%

Understanding the Mechanism of Cell Death in Gemcitabine Resistant Pancreatic Ductal Adenocarcinoma: A Systems Biology Approach

Aier

Varadwaj

2020

Self Cite

View full text Add to dashboard Cite

Background: Gemcitabine is the standard chemotherapeutic drug administered in advanced Pancreatic Ductal Adenocarcinoma (PDAC). However, due to drug resistance in PDAC patients, this treatment has become less effective. Over the years, clinical trials for the quest of finding novel compounds that can be used in combination with gemcitabine have met very little success. Objective: To predict the driving factors behind pancreatic ductal adenocarcinoma, and to understand the effect of these components in the progression of the disease and their contribution to cell growth and proliferation. Methods: With the help of systems biology approaches and using gene expression data, which is generally found in abundance, dysregulated elements in key signalling pathways were predicted. Prominent dysregulated elements were integrated into a model to simulate and study the effect of gemcitabine- induced hypoxia. Results: In this study, several transcription factors in the form of key drivers of cancer-related genes were predicted with the help of CARNIVAL, and the effect of gemcitabine-induced hypoxia on the apoptosis pathway was shown to have an effect on the downstream elements of two primary pathway models; EGF/VEGF and TNF signalling pathway. Conclusion: It was observed that EGF/VEGF signalling pathway played a major role in inducing drug resistance through cell growth, proliferation, and avoiding cell death. Targeting the major upstream components of this pathway could potentially lead to successful treatment.

show abstract

A systematic assessment of statistics, risk factors, and underlying features involved in pancreatic cancer

Cited by 103 publications

References 48 publications

Long noncoding RNA LINC00514 accelerates pancreatic cancer progression by acting as a ceRNA of miR-28-5p to upregulate Rap1b expression

Long noncoding RNA LINC00514 accelerates pancreatic cancer progression by acting as a ceRNA of miR-28-5p to upregulate Rap1b expression

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Understanding the Mechanism of Cell Death in Gemcitabine Resistant Pancreatic Ductal Adenocarcinoma: A Systems Biology Approach

Contact Info

Product

Resources

About