Micro<scp>RNA</scp>‐135a acts as a putative tumor suppressor by directly targeting very low density lipoprotein receptor in human gallbladder cancer

Zhou, Huading; Guo, Weijie; Zhao, Yingjun; Wang, Yifei; Zha, Rujing; Ding, Jie; Liang, Linhui; Yang, Guanghua; Chen, Zongyou; Ma, Baojin; Yin, Baobing

doi:10.1111/cas.12463

Cited by 75 publications

(70 citation statements)

References 20 publications

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“…Thus, it might be a better resolution to establish more-accurate prognostic gene signatures by using a combination of different types of transcripts (24). A growing volume of literature has demonstrated that noncoding RNAs, predominantly miRNAs, could serve as potential biomarkers of gallbladder cancer (3,25). Given the fact that lncRNAs are more abundantly expressed in mammalian cells, it is plausible to speculate that lncRNAs, once regarded as "transcriptional noise," may be potential prognostic indicators in gallbladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

et al. 2016

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Long noncoding RNAs (lncRNA) are being implicated in the development of many cancers. Here, we report the discovery of a critical role for the lncRNA GCASPC in determining the progression of gallbladder cancer. Differentially expressed lncRNAs and mRNAs between gallbladder cancer specimens and paired adjacent nontumor tissues from five patients were identified and validated by an expression microarray analysis. Quantitative real-time PCR was used to measure GCASPC levels in tissues from 42 gallbladder cancer patients, and levels of GCASPC were confirmed further in a separate cohort of 89 gallbladder cancer patients. GCASPC was overexpressed or silenced in several gallbladder cancer cell lines where molecular and biological analyses were performed. GCASPC levels were significantly lower in gallbladder cancer than adjacent nontumor tissues and were associated with tumor size, American Joint Committee on Cancer tumor stage, and patient outcomes. GCASPC overexpression suppressed cell proliferation in vitro and in vivo, whereas GCASPC silencing had opposite effects. By RNA pull-down and mass spectrometry, we identified pyruvate carboxylase as an RNAbinding protein that associated with GCASPC. Because GCASPC is a target of miR-17-3p, we confirmed that both miR-17-3p and GCASPC downregulated pyruvate carboxylase level and activity by limiting protein stability. Taken together, our results defined a novel mechanism of lncRNA-regulated cell proliferation in gallbladder cancer, illuminating a new basis for understanding its pathogenicity. Cancer Res; 76(18); 5361-71. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

et al. 2016

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“…Furthermore, the transfection of a miRNA135a-5p mimetic inhibited proliferation and colony formation of GBC cells by G1/S phase cell-cycle block; lentivirus-mediated overexpression of miRNA-135a signiicantly reduced the proliferation of GBC cells. In addition, xenografts from miRNA-135a-infected cells in nude mice were signiicantly smaller compared to controls [9]. These evidences suggested the oncosuppressive role of this miRNA in GBC.…”

Section: Onco-suppressor Mirnas In Gallbladder Cancermentioning

confidence: 86%

“…Its levels have been found to be signiicantly downregulated in GBC tissues and were correlated with the histological grade of the tumors [9]. Furthermore, the transfection of a miRNA135a-5p mimetic inhibited proliferation and colony formation of GBC cells by G1/S phase cell-cycle block; lentivirus-mediated overexpression of miRNA-135a signiicantly reduced the proliferation of GBC cells.…”

Section: Onco-suppressor Mirnas In Gallbladder Cancermentioning

confidence: 99%

Noncoding RNAs in Gallbladder Cancer

Paliogiannis¹,

Latte²,

Imam³

2017

Updates in Gallbladder Diseases

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Gallbladder cancer (GBC) is the most frequent malignancy of the biliary tract, representing about 85-90% of the cancers involving this anatomical district; it is characterized by high mortality rates with less than 10% of the suferers surviving more than 5 years. Extensive scientiic research is needed in order to identify biomarkers for early diagnosis, improve the treatment options available, and assess new efective therapies. Consistent improvements have been made in recent years in the ield of noncoding RNAs. More than 90% of the human genome is constituted by a noncoding portion that actively transcribes an enormous and complex amount of RNA, while only approximately 2% represents the coding genes. Noncoding RNAs are divided into two categories in accordance with their dimensions: small RNAs, which are made by less than 200 nucleotides, and long RNAs, which are bigger. MicroRNAs (miRNAs) and long noncoding RNA (lncRNAs) are the main subclasses, respectively, which concentrate consistent scientiic eforts in recent times with promising results in several diseases, including cancer. In this review, we summarize the roles of miRNAs and lncRNAs in gallbladder cancer pathophysiology and their possible translational implication in the diagnosis and treatment of this aggressive disease.

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“…miRNA expression profiling has been performed by large-scale microarray analysis in GBC tissues or cells in several studies (26,(46)(47)(48). Numerous miRNAs exhibit expression changes, with some miRNAs being upregulated, but most being downregulated in GBC cells and tissues.…”

Section: Micrornas and Gbcsmentioning

confidence: 99%

“…These data provide proof that miR-135a-5p may inhibit the proliferation of GBC cells in vitro and in vivo. Furthermore, it was demonstrated that miR-135a exhibited this function through directly binding the 3'-UTR of very low-density lipoprotein receptor, thus resulting in activation of the p38 mitogen-activated protein kinase pathway (47).…”

Section: Tumor Suppressor Micrornasmentioning

confidence: 99%

The role of microRNAs in gallbladder cancer

Yang

Zhang

et al. 2016

Molecular and Clinical Oncology

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Abstract. MicroRNAs (also referred to as miRNAs or miRs) play a crucial role in post-transcriptional gene regulation and serve as negative gene regulators by controlling a variety of target genes and regulating diverse biological processes, such as cell proliferation, invasion, migration and apoptosis. Aberrant expression of miRNAs is associated with the development and progression of cancer. Recent studies have reported that miRNAs may repress or promote the expression of cancer-related genes via several different signaling pathways in gallbladder cancer (GBC) patients and may function as tumor suppressors or oncogenes, thus providing a promising tool for the diagnosis and therapeutics of GBCs. In this review, we summarize the role of dysregulawted miRNA expression in the signaling pathways implicated in GBC and discuss the significant role of circulating miRNAs in GBC. Therefore, miRNAs may serve as novel therapeutic targets as well as diagnostic or prognostic markers in GBC.

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MicroRNA‐135a acts as a putative tumor suppressor by directly targeting very low density lipoprotein receptor in human gallbladder cancer

Cited by 75 publications

References 20 publications

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase–Dependent Cell Proliferation in Gallbladder Cancer

Noncoding RNAs in Gallbladder Cancer

The role of microRNAs in gallbladder cancer

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