Long non-coding RNA UCA1 indicates an unfavorable prognosis and promotes tumorigenesis via regulating AKT/GSK-3β signaling pathway in cholangiocarcinoma

Xu, Yi; Yao, Yongliang; Leng, Kaiming; Li, Zhenglong; Qin, Wei; Zhong, Xian; Kang, Pengcheng; Wu, Ming; Jiang, Xingming; Cui, Yunfu

doi:10.18632/oncotarget.21884

Cited by 44 publications

(46 citation statements)

References 38 publications

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“…Recent literatures have mainly focused on the expression pattern and the function of lncRNA UCA1 in various cancers, and the pivotally regulatory role of lncRNA UCA1 in cancer cells proliferation, invasion, migration, and apoptosis has been widely reported [13,14,17]. Besides, although the underling mechanisms of which lncRNA UCA1 functioned to malignant growth and metastasis are still a mystery, bioinformatics analyses have suggested that it might be by sponging miRNAs, and thereby quarantining the target gene of miRNAs from degradation [15].…”

Section: Introductionmentioning

confidence: 99%

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Yin

Sun

2018

Cell Physiol Biochem

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Background/Aims: Recent studies have suggested that several lncRNAs contribute to the angiogenic function of endothelial cells. Herein, we set out to reveal whether lncRNA UCA1 has functions in endothelial angiogenesis. Methods: The expression levels of lncRNA UCA1, miR-195 and CCND1 in human microvascular endothelial HMEC-1 cells were altered by transfection. Subsequently, cell viability, migration, tube formation and apoptosis of HMEC-1 cells were respectively assessed. The cross-talk between lncRNA UCA1, miR-195, CCND1, and MEK/ERK and mTOR signaling pathways were investigated by performing qRT-PCR and Western blotting. Results: Silence of lncRNA UCA1 repressed HMEC-1 cells viability, migration, tube formation, and induced apoptosis. Meanwhile, silence of lncRNA UCA1 significantly up-regulated miR-195 expression. These alterations induced by lncRNA UCA1 were further enhanced by miR-195 overexpression, while were attenuated by miR-195 suppression. Moreover, silence of lncRNA UCA1 deactivated MEK/ERK and mTOR signaling pathways via a miR-195-dependent regulation. And the deactivation of MEK/ERK and mTOR signaling pathways led to a down-regulation of CCND1. Conclusion: This study demonstrates that silence of lncRNA UCA1 largely represses microvascular endothelial cells growth and tube formation. Silence of lncRNA UCA1 exerts its function possibly via up-regulation of miR-195, which in turn inactivates MEK/ERK and mTOR signaling pathways, and ultimately represses CCND1 expression.

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Section: Introductionmentioning

confidence: 99%

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Yin

Sun

2018

Cell Physiol Biochem

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“…For instance, upregulated lncRNA Sox2ot is related with lymph node invasion (P=0.0308), TNM stage (P=0.0072) and postoperative recurrence (P=0.0019) [29]. Besides, both lncRNA UCA1(urothelial carcinoma associated 1) and CCAT1 involve in CCA clinicopathological conditions [30][31][32]. Interestingly, the upregulation of lncRNA CPS1-IT1 is associated with poorer liver function [33].…”

Section: Lncrna Is Abnormally Expressed In Cca Tissuesmentioning

confidence: 99%

“…For instance, Xia, X. L. et al silenced a colorectal-cancer-related lncRNA CRNDE and observed E-cadherin was significantly increased, while N-cadherin and Vimen-tin were lost in ICC cell lines [54]. LncRNA UCA1 also can promote EMT formation [32]. When silencing UCA1, Vimentin and N-cadherin were decreased with enhanced expression of E-cadherin.…”

Section: Lncrna Promotes Emt In Cca Developmentmentioning

confidence: 99%

“…The phosphatidylinositol 3-kinase(PI3K)/AKT pathway is a key driver in carcinogenesis, modulating cell survival, differentiation, angiogenesis, and cellular migration [55]. LncRNA UCA1 promotes CCA progression by activating AKT/GSK-3β/CCND1 signaling pathway [32]. Knockdown of UCA1 in CCA cell lines, phosphorylated-AKT and phosphorylated-GSK-3β decreased, which further inhibiting the expression of CCND1.…”

Section: Lncrna Activates Oncogenic Signaling Pathways In Cca Developmentioning

confidence: 99%

“…The high expression of lncRNA CCAT1 could be an independent unfavorable prognostic biomarker for CCA [30]. LncRNA UCA1 is also an independent prognostic factor for CCA overall survival (P = 0.014) [32]. The high expression of host gene CPS1 and its associated lncRNA CPS1-IT1 serves as a poor prognostic marker in ICC [33].…”

Section: Lncrna Serves As Potential Diagnostic or Prognostic Markersmentioning

confidence: 99%

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The Advancement of Long Non-Coding RNAs in Cholangiocarcinoma Development

Jiang¹,

Ling²

2019

J. Cancer

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Cholangiocarcinoma (CCA) is a malignancy with increasing incidence in recent years. CCA patients are usually diagnosed at advanced stage due to lack of apparent symptoms and specifically diagnostic markers. Nowadays, surgical removal is the only effective method for CCA whereas overall 5-year-survival rate keeps around 10%. Long-noncoding RNA (lncRNA), a subtype of noncoding RNA, is widely studied to be abnormally expressed in multiple cancers including CCA. LncRNA can promote proliferation, migration, invasion and inhibit apoptosis of CCA. Moreover, lncRNA is negatively correlated with the prognosis of CCA. LncRNA may contribute to the development of CCA via modulating gene transcription, sponging microRNA, regulating CCA-related signaling pathways or protein expression. LncRNA is thought to be potential diagnostic markers and therapeutic targets for CCA.

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

Yang

Deng

et al. 2020

Cancer Communications

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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.

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Long non-coding RNA UCA1 indicates an unfavorable prognosis and promotes tumorigenesis via regulating AKT/GSK-3β signaling pathway in cholangiocarcinoma

Cited by 44 publications

References 38 publications

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

The Advancement of Long Non-Coding RNAs in Cholangiocarcinoma Development

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

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