Emerging roles of long noncoding RNAs in cholangiocarcinoma: Advances and challenges

Abstract

Cholangiocarcinoma (CCA), a cancer with a relatively low incidence rate, is usually associated with poor prognosis. Current modalities for the diagnosis and treatment of CCA patients are still far from satisfactory. In recent years, numerous long noncoding RNAs (lncRNAs) have been identified as crucial players in the development of various cancers, including CCA. Abnormally expressed lncRNAs in CCA, regulated by some upstream molecules, significantly influence the biological behavior of tumor cells and are involved in tumor development through various mechanisms, including interactions with functional proteins, participation in competing for endogenous RNA (ceRNA) regulatory networks, activation of cancer‐related signaling pathways and epigenetic modification of gene expression. Furthermore, several lncRNAs are closely associated with the clinicopathological features of CCA patients, and are promising biomarkers for diagnosing and prognostication of CCA. Some of these lncRNAs play an important role in chemotherapy drug resistance. In addition, lncRNAs have also been shown to be involved in the inflammation microenvironment of CCA and malignant outcome of CCA risk factors, such as cholestatic liver diseases. In view of the difficulty of diagnosing CCA, more attention should be paid to detectable lncRNAs in the serum or bile. This review summarizes the recent knowledge on lncRNAs in CCA and provides a new outlook on the molecular mechanisms of CCA development from the perspective of lncRNAs. Moreover, we also discussed the limitations of the current studies and differential expression of lncRNAs in different types of CCA.

LINC00630 promotes cholangiocarcinoma cell proliferation, migration and invasion by mediating the miR-199a/FGF7 axis

“…Due to its unclear molecular mechanisms, current clinical diagnosis and treatment for CCA remain unsatisfactory. A large body of recent research has shown that lncRNAs play critical roles in the occurrence and development of various types of cancer [10,11], including CCA [12]. lncRNAs have been implicated in the splicing, export and translation of mRNAs and regulate the stability and post-translational modification of target proteins.…”

Identification of a competing endogenous RNA axis “SVIL‐AS1/miR‐103a/ICE1” associated with chemoresistance in lung adenocarcinoma by comprehensive bioinformatics analysis

“…Competing endogenous RNA is an important mechanism for lncRNA to regulate cancer progression and chemoresistance. 29,30 To better understand the regulation mechanism of genes on chemoresistance, a ceRNA axis (SVIL-AS1/miR-103a/ICE1) was constructed based on the key chemotherapyrelated module. Kaplan-Meier survival analysis of genes in SVIL-AS1/miR-103a/ICE1 axis showed that in the LUAD patients receiving chemotherapy, high expression of SVIL-AS1 and ICE1 corresponded to a better prognosis, while high expression of miR-103a corresponded to a poor prognosis.…”

Identification and Validation of lncRNA-Related Prognostic Signatures in Cholangiocarcinoma

“…In addition to its insidious onset, CCA is also characterized by high malignancy and early recurrence [23][24][25]28] . Studies have reported that lncRNAs are crucial regulators of diverse biological processes of mRNA and play essential roles in tumorigenesis [29][30][31][32] . Therefore, in this study, we aimed at identifying prognostic-related DElncRNAs in CCA and validated their effects on CCA tumorigenesis and progression.…”