Abstract
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.
Highlights
Despite the recent advancement in cancer research, cancer is among the most commonly occurring diseases and one of the primary causes of death globally [1,2,3,4,5]
Several studies have demonstrated the close association of different regulatory noncoding RNAs (ncRNAs) such as circRNAs, long noncoding RNAs (lncRNAs), miRNAs, and small nucleolar RNAs (snoRNA) in the initiation and progression of Gall bladder cancer (GBC) (Figure 1) [21,22,23,24]
Studies have reported the oncogenic role of lncRNA high expressed in gallbladder cancer (HEGBC) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in GBC through modulation of IL-11/STAT3 and ERK/MAPK signaling pathway, respectively [23,57]
Summary
Despite the recent advancement in cancer research, cancer is among the most commonly occurring diseases and one of the primary causes of death globally [1,2,3,4,5]. Studies have revealed that they involve a network of internal signals that control the expression of numerous genes regulating the physiological and developmental processes Evidence suggests that these regulatory ncRNAs play a vital role in epigenetic control [14,15]. Several studies have demonstrated the close association of different regulatory ncRNAs such as circRNAs, lncRNAs, miRNAs, and snoRNAs in the initiation and progression of GBC (Figure 1) [21,22,23,24]. One study has reported the positive correlation between the augmented expression of circular–mitochondrial translation optimization 1 (circ-MTO1) in the plasma of GBC patients and poor progression-free and overall survival [27] Another circRNA, circFOXP1, was reported to be upregulated in GBC and was found to regulate the expression of pyruvate kinase, liver, and RBC (PKLR) by sponging miR-370. Several studies have reported their role as oncogenes and tumor suppressors in GBC [21,51]
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