The Advancement of Long Non-Coding RNAs in Cholangiocarcinoma Development

Jiang, Fengru; Ling, Xiaofeng

doi:10.7150/jca.32411

Cited by 22 publications

(17 citation statements)

References 74 publications

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“…One of the main regulatory functions of lncRNAs is to act as competing endogenous RNAs (ceRNAs) to sponge miRNAs, leading to the loss of the ability to degrade, silence, or hamper translation of their downstream genes 17 . Many lncRNAs have been shown to regulate key factors involved in cancer cells 18 and some of them represent potential diagnostic markers and therapeutic targets for CCA 19 , 20 . Therefore, we carried out the present study to explore potential upstream lncRNAs that can regulate the miR-320a/NRP-1 axis in CCA.…”

Section: Introductionmentioning

confidence: 99%

LncRNA TTN-AS1 promotes the progression of cholangiocarcinoma via the miR-320a/neuropilin-1 axis

Zhu

Zhai

et al. 2020

Cell Death Dis

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Neuropilin-1 regulated by miR-320a participates in the progression of cholangiocarcinoma by serving as a co-receptor that activates multiple signaling pathways. The present study sought to investigate upstream lncRNAs that control the expression of miR-320a/neuropilin-1 axis and dissect some of the underlying mechanisms. Here we report lncRNA TTN-AS1 (titin-antisense RNA1) acts as a sponging ceRNA to downregulate miR-320a and is highly expressed in human cholangiocarcinoma tissues and cells. The expression of the above three molecules is correlated with the clinicopathologic parameters of cholangiocarcinoma patients. In this study, multiple bioinformatics tools and databases were employed to seek potential lncRNAs that have binding sites with miR-320a and TTN-AS1 was identified because it exhibited the largest folds of alteration between cholangiocarcinoma and normal bile duct epithelial cells. The regulatory role of TTN-AS1 on miR-320a was further evaluated by luciferase reporter and RNA pulldown assays, coupled with in situ hybridization and RNA immunoprecipitation analyses, which showed that TTN-AS1 bound to miR-320a through an argonaute2-dependent RNA interference pathway in the cytoplasm of cholangiocarcinoma cells. Knockdown and overexpression assays showed that the regulatory effect between TTN-AS1 and miR-320 was in a one-way manner. TTN-AS1 promoted the proliferation and migration of cholangiocarcinoma cells via the miR-320a/ neuropilin-1 axis. The function of TTN-AS1 on tumor growth and its interaction with miR-320a were confirmed in animal models. Further mechanistic studies revealed that TTA-AS1, through downregulating miR-320a, promoted cell cycle progression, epithelial-mesenchymal transition, and tumor angiogenesis by upregulating neuropilin-1, which co-interacted with the hepatocyte growth factor/c-Met and transforming growth factor (TGF)-β/ TGF-β receptor I pathways. In conclusion, the present results demonstrate that lncRNA TTA-AS1 is a sponging ceRNA for miR-320a, which in turn downregulates neuropilin-1 in cholangiocarcinoma cells, indicating these three molecules represent potential biomarkers and therapeutic targets in the management of cholangiocarcinoma.

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Section: Introductionmentioning

confidence: 99%

LncRNA TTN-AS1 promotes the progression of cholangiocarcinoma via the miR-320a/neuropilin-1 axis

Zhu

Zhai

et al. 2020

Cell Death Dis

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“…As in HCC and ICC, non-coding alterations are common in cHCC-ICC, for example large cohorts have shown 22.9% of cases with TERT promoter mutations and 29.7% of cases with NEAT1 (an intergenic non-coding RNA gene for a long noncoding RNA) alterations, but detailed comparisons to HCC and ICC and how to target these changes therapeutically are not yet clear (19,(48)(49)(50).…”

Section: Genetic Characterization and Molecular Biologymentioning

confidence: 99%

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

et al. 2020

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Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.

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“…This review introduces selected studies of lncRNAs in CCA especially from recent studies. For other lncRNAs in CCA, see previous schematic reviews (43,44).…”

Section: Cholangiocarcinoma Lncrnas As Competing Endogenous Rnas In Ccamentioning

confidence: 99%

Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies

et al. 2020

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Long non-coding RNAs (lncRNAs) are RNAs with lengths exceeding 200 nucleotides that are not translated into proteins. It is well-known that small non-coding RNAs, such as microRNAs (miRNAs), regulate gene expression and play an important role in cholangiopathies. Recent studies have demonstrated that lncRNAs may also play a key role in the pathophysiology of cholangiopathies. Patients with cholangiopathies often develop cholangiocarcinoma (CCA), which is cholangiocyte-derived cancer, in the later stage. Cholangiocytes are a primary target of therapies for cholangiopathies and CCA development. Previous studies have demonstrated that expression levels of lncRNAs are altered in the liver of cholangiopathies or CCA tissues. Some lncRNAs regulate gene expression by inhibiting functions of miRNAs leading to diseased liver conditions or CCA progression, suggesting that lncRNAs could be a novel therapeutic target for those disorders. This review summarizes current understandings of functional roles of lncRNAs in cholangiopathies and seek their potentials for novel therapies.

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The Advancement of Long Non-Coding RNAs in Cholangiocarcinoma Development

Cited by 22 publications

References 74 publications

LncRNA TTN-AS1 promotes the progression of cholangiocarcinoma via the miR-320a/neuropilin-1 axis

LncRNA TTN-AS1 promotes the progression of cholangiocarcinoma via the miR-320a/neuropilin-1 axis

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies

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