Reiterating the Emergence of Noncoding RNAs as Regulators of the Critical Hallmarks of Gall Bladder Cancer

Gall bladder cancer (GBC) is a rare and one of the most aggressive types of malignancies, often associated with a poor prognosis and survival. It is a highly metastatic cancer and is often not diagnosed at the initial stages, which contributes to a poor survival rate of patients. The poor diagnosis and chemoresistance associated with the disease limit the scope of the currently available surgical and nonsurgical treatment modalities. Thus, there is a need to explore novel therapeutic targets and biomarkers that will help relieve the severity of the disease and lead to advanced therapeutic strategies. Accumulating evidence has correlated the atypical expression of various noncoding RNAs (ncRNAs), including circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNA) with the increased cell proliferation, epithelial–mesenchymal transition (EMT), invasion, migration, metastasis, chemoresistance, and decreased apoptosis in GBC. Numerous reports have indicated that the dysregulated expression of ncRNAs is associated with poor prognosis and lower disease-free and overall survival in GBC patients. These reports suggest that ncRNAs might be considered novel diagnostic and prognostic markers for the management of GBC. The present review recapitulates the association of various ncRNAs in the initiation and progression of GBC and the development of novel therapeutic strategies by exploring their functional and regulatory role.

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PCBP1 is an important mediator of TGF-β-induced epithelial to mesenchymal transition in gall bladder cancer cell line GBC-SD

Molecular Biology Reports ◽

10.1007/s11033-014-3428-7 ◽

2014 ◽

Vol 41 (8) ◽

pp. 5519-5524 ◽

Cited By ~ 10

Author(s):

Hang-Yu Zhang ◽

Ke-Feng Dou

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Cell Line ◽

Cancer Cell ◽

Epithelial To Mesenchymal Transition ◽

Cancer Cell Line ◽

Gall Bladder Cancer ◽

Bladder Cancer Cell Line ◽

Mesenchymal Transition ◽

Important Mediator

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Liver cancer

10.1093/med/9780199568741.003.0218 ◽

2018 ◽

Author(s):

Satish Keshav ◽

Palak Trivedi

Keyword(s):

Bladder Cancer ◽

Liver Cancer ◽

Gall Bladder ◽

Metastatic Cancer ◽

Gall Bladder Cancer ◽

Sub Saharan Africa ◽

Primary Hepatocellular Carcinoma ◽

Solid Organ ◽

The West ◽

Liver Cancers

Primary hepatocellular carcinoma (HCC) arises from hepatocytes and is one of the commonest solid-organ malignancies in the world, particularly in the Far East and in sub-Saharan Africa. Cholangiocarcinoma arises from the biliary epithelium. The incidence is rising in the West, and primary sclerosing cholangitis (PSC) is an important risk factor (15% lifetime risk). Other forms of liver cancer include metastatic cancer, which is much more common in the West than any primary liver cancer, accounting for 90% of liver cancers and for which common primary sites are the colon, the stomach, the breasts, and the lungs; hepatoblastoma, which is an uncommon malignancy in children, originating from immature liver cell precursors; haemangiosarcomas, which are also rare, are malignant tumours arising from the blood vessels in the liver and can be very rapidly growing; and gall bladder cancer, arising from the gall bladder epithelium. Gallstones and PSC are risk factors for gall bladder cancer; in particular, PSC confers a risk >160 times that of the control population. This chapter primarily focuses on HCC.

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Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190725122400 ◽

2020 ◽

Vol 19 (16) ◽

pp. 2019-2033 ◽

Cited By ~ 2

Author(s):

Pratibha Pandey ◽

Mohammad H. Siddiqui ◽

Anu Behari ◽

Vinay K. Kapoor ◽

Kumudesh Mishra ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cell Growth ◽

Gall Bladder ◽

Growth Inhibition ◽

Cell Cycle Arrest ◽

Gall Bladder Cancer ◽

Cell Growth Inhibition ◽

Cycle Arrest ◽

Apoptotic Induction

Background: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. Objective: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. Methods: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. Results: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5μM) in combination with Jab1-siRNA. Conclusion: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of gall bladder cancer.

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Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190206124120 ◽

2019 ◽

Vol 19 (6) ◽

pp. 826-837 ◽

Cited By ~ 3

Author(s):

Pratibha Pandey ◽

Preeti Bajpai ◽

Mohammad H. Siddiqui ◽

Uzma Sayyed ◽

Rohit Tiwari ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Gall Bladder ◽

Cancer Cells ◽

Caspase 3 ◽

Annexin V ◽

Gall Bladder Cancer ◽

Apoptosis Induction ◽

Bladder Cancer Cells ◽

Hoechst Staining

Background:Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.Objective:In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.Methods:In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.Results:Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.Conclusion:Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

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Anatomical segment 4b/5 resection for gall bladder cancer using intraoperative ultrasound

Journal of Visceral Surgery ◽

10.1016/j.jviscsurg.2021.04.003 ◽

2021 ◽

Author(s):

S. Singh ◽

S. Goel ◽

A. Iqbal

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Intraoperative Ultrasound ◽

Gall Bladder Cancer

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Descriptive epidemiology of gall-bladder cancer in Europe

Journal of Cancer Research and Clinical Oncology ◽

10.1007/bf01229532 ◽

1993 ◽

Vol 119 (3) ◽

pp. 165-171 ◽

Cited By ~ 29

Author(s):

Witold Zatonskí ◽

Carlo La Vecchia ◽

Fabio Levi ◽

Eva Negri ◽

Franca Lucchini

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Gall Bladder Cancer ◽

Descriptive Epidemiology

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Role of Combination Chemotherapy with 5-Fluorouracil, Cisplatin and Paclitaxel for Advanced Gall Bladder Cancer

Journal of Cancer Therapy ◽

10.4236/jct.2014.53032 ◽

2014 ◽

Vol 05 (03) ◽

pp. 246-252 ◽

Cited By ~ 1

Author(s):

Mumtaz Ahmad Ansari ◽

Satyendra K. Tiwary ◽

Uday Pratap Shahi ◽

Vijay K. Shukla

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Combination Chemotherapy ◽

Gall Bladder Cancer ◽

Advanced Gall Bladder Cancer

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The role of H. pylori infection in gall bladder cancer: clinicopathological study

Tumor Biology ◽

10.1007/s13277-015-3444-9 ◽

2015 ◽

Vol 36 (9) ◽

pp. 7093-7098 ◽

Cited By ~ 10

Author(s):

Ehsan Hassan Hassan ◽

Shawkat S. Gerges ◽

Kamal A. El-Atrebi ◽

Hala T. El-Bassyouni

Keyword(s):

Bladder Cancer ◽

Gall Bladder ◽

Gall Bladder Cancer ◽

Clinicopathological Study ◽

H Pylori

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Biological functions and clinical significance of long noncoding RNAs in bladder cancer

Cell Death Discovery ◽

10.1038/s41420-021-00665-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yan Zhang ◽

Xianwu Chen ◽

Juntao Lin ◽

Xiaodong Jin

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Noncoding Rna ◽

Epithelial Mesenchymal Transition ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Research Progress ◽

High Morbidity ◽

Biological Functions ◽

Mesenchymal Transition

AbstractBladder cancer (BCa) is one of the 10 most common cancers with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNAs), a large class of noncoding RNA transcripts, consist of more than 200 nucleotides and play a significant role in the regulation of molecular interactions and cellular pathways during the occurrence and development of various cancers. In recent years, with the rapid advancement of high-throughput gene sequencing technology, several differentially expressed lncRNAs have been discovered in BCa, and their functions have been proven to have an impact on BCa development, such as cell growth and proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug-resistance. Furthermore, evidence suggests that lncRNAs are significantly associated with BCa patients’ clinicopathological characteristics, especially tumor grade, TNM stage, and clinical progression stage. In addition, lncRNAs have the potential to more accurately predict BCa patient prognosis, suggesting their potential as diagnostic and prognostic biomarkers for BCa patients in the future. In this review, we briefly summarize and discuss recent research progress on BCa-associated lncRNAs, while focusing on their biological functions and mechanisms, clinical significance, and targeted therapy in BCa oncogenesis and malignant progression.

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