Long non-coding RNA LOC389641 promotes progression of pancreatic ductal adenocarcinoma and increases cell invasion by regulating E-cadherin in a TNFRSF10A-related manner

Zheng, Shusen; Chen, Huimou; Wang, Yingxue; Gao, Wenchao; Fu, Zhiqiang; Zhou, Quanbo; Jiang, Yanjun; Q, Lin; Tan, Langping; Ye, Huilin; Zhao, Xiaohui; Luo, Yuming; Li, Guolin; Ye, Liangtao; Liu, Yimin; Li, Wenzhu; Li, Zhihua; Chen, Rufu

doi:10.1016/j.canlet.2015.12.010

Cited by 60 publications

(54 citation statements)

References 43 publications

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“…Previous studies have shown a variety of interactions between lncRNAs and proteins, for instance, LOC389641 with E-cadherin [21], SNHG5 with MTA2 [22], and CASC11 with hnRNP-K [23]. In this study, a significant positive expression correlation between lnc-GNAT1-1 and RKIP was detected.…”

Section: Discussionsupporting

confidence: 64%

A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit

Shen

Wang

et al. 2016

J Exp Clin Cancer Res

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BackgroundThe role of long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) progression has not fully been elucidated. This study was designed to report the identification of a novel lncRNA, lnc-GNAT1-1, and its functional role in CRC progression.MethodslncRNA expression profile microarray was performed in three paired primary and liver metastatic tissues of CRC, and a novel lncRNA, lnc-GNAT1-1, was identified to be a potential functional lncRNA. Quantitative real-time PCR was used to detect its expression in CRC tissues, cell lines, and patients’ plasma, cell fractionation was used to evaluate its subcellular location. lnc-GNAT1-1 was knockdown by siRNA or overexpressed by a lentivirus vector, then in vitro an vivo experiments were performed to evaluate its biological role and the underlying mechanisms in CRC.ResultsExpression of lnc-GNAT1-1 was decreased in liver metastasis than the primary tumor, while the later one is lower than the paired normal mucosa. Decreased lnc-GNAT1-1 expression was associated unfavorable clinicopathological features and a poor prognosis of CRC patients. In multivariate analysis, lnc-GNAT1-1 was proved to be an independent prognostic factor. In plasma, lnc-GNAT1-1 was significant decreased in CRC patients than healthy donors, and with the TNM stages advanced, the plasma lnc-GNAT1-1 level decreased; Receiver operating characteristic curve (ROC curve) showed that plasma lnc-GNAT1-1 had a moderate to well diagnostic efficiency for CRC. In vitro experiments showed that knockdown of lnc-GNAT1-1 could inhibit the aggressive phenotypes of CRC cell lines. In vivo study showed that overexpression of lnc-GNAT1-1 could suppress the liver metastasis of CRC cells. Finally, we explored the underlying mechanism of the role lnc-GNAT1-1 plays in CRC, and found a positive correlation between lnc-GNAT1-1 and Raf kinase inhibitor protein (RKIP) expression both in cells and in patients’ tissues. We further found that lnc-GNAT1-1 could regulate the RKIP-NF-κB-Snail circuit in CRC.ConclusionsWe have demonstrated in this study that a novel lncRNA, lnc-GNAT1-1, is low expressed in colorectal cancer tissues and plasma, and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0467-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 64%

A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit

Shen

Wang

et al. 2016

J Exp Clin Cancer Res

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“…Furthermore, miR-501-3p possibly promoted cancer invasion via down-regulating E-cadherin, which is well known as a transmembrane protein localized to the adherence junctions of the epithelial cell basolateral surface that plays a key role in epithelial morphology maintenance. The loss of E-cadherin expression is a well-recognized marker of EMT, and it promotes PDAC progression, invasion and metastasis [15]. Taken together, our results indicate that the lower expression of miR-501-3p in pancreatic body/tail cancer might be associated with the higher expression of E-cadherin, and subsequently, a less invasive/metastasis phenotype compared with pancreatic head cancer.…”

Section: Discussionmentioning

confidence: 53%

The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma

Ling

et al. 2017

Oncotarget

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Different clinical presentations and prognoses have been implied between pancreatic head and body/tail cancers. We aimed to identify the prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). Thirty-two pairs of patients with strictly matched early stage (II) pancreatic head and body/tail cancers were enrolled. The molecular feature of the two subtypes of PDAC was assessed on the level of miRNA expression. Out of the 64 patients, 34 (53.1%) had tumor recurrence after radical resection during the follow-up period (2.3 ± 0.8 years). Both overall and tumor-free survival were significantly higher in the patients with pancreatic body/tail cancer compared with those with pancreatic head cancer. Patient age and tumor location were the independent prognostic factors for tumor recurrence. A remarkably lower expression of miR-501-3p and higher expression of miR-375 were found and were further verified in pancreatic body/tail cancer tissues compared with pancreatic head cancer tissues. The low expression of miR-501-3p was significantly associated with a low risk of tumor recurrence. Both, subcutaneous and orthotopic PDAC mouse models presented highly invasive tumor phenotypes upon up-regulated miR-501-3p expression. An in vitro study showed that miR-501-3p promoted the invasiveness of PDAC cells possibly via suppressing E-cadherin. In summary, at resectable early stage, pancreatic body/tail cancer presents a less malignant phenotype associated with deregulation of miR-501-3p compared with pancreatic head cancer.

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“…Additionally, lncRNA-NUTF2P3-001 contributes to PCa proliferation and invasion by derepressing the miR-3923/KRAS pathway [19]. Moreover, LOC389641 promotes progression of pancreatic ductal adenocarcinoma and increases cell invasion by regulating E-cadherin with the possible involvement of TNFRSF10A [20]. Insights from such studies have provided evidence that lncRNAs enhance PCa cell proliferation, malignant transformation and metastasis, and that lncRNA regulatory processes are critical players in PCa tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for pancreatic cancer

Zhang

Chen

et al. 2016

Oncotarget

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Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a long noncoding RNA (lncRNA) that regulates tumor cell viability and proliferation. We used qRT-PCR and RNA FISH analysis to evaluate Linc-pint levels in the plasma and tumor tissues of pancreatic cancer (PCa) patients. Our data demonstrate that Linc-pint expression is lower in plasma samples from PCa patients than from healthy individuals, and indicate that plasma Linc-pint levels are more sensitive than CA19-9 for detecting PCa. Our data also show that Linc-pint levels are lower in PCa tumors than in adjacent tissues, carcinoma of the ampulla of Vater (CAV) and cholangiocarcinoma (CCA), and suggest that Linc-pint could be used for distinguishing the cause of malignant obstructive jaundice. Low plasma Linc-pint levels correlate with tumor recurrence, while low tumor Linc-pint levels correlate with poor prognosis for PCa patients after pancreatectomy. These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis.

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Long non-coding RNA LOC389641 promotes progression of pancreatic ductal adenocarcinoma and increases cell invasion by regulating E-cadherin in a TNFRSF10A-related manner

Cited by 60 publications

References 43 publications

A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit

A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit

The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma

Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for pancreatic cancer

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