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LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis.

ABSTRACT: Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.

SUBMITTER: Wu XS

PROVIDER: S-EPMC5623869 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis.

Wu Xiang-Song XS Wang Fang F Li Huai-Feng HF Hu Yun-Ping YP Jiang Lin L Zhang Fei F Li Mao-Lan ML Wang Xu-An XA Jin Yun-Peng YP Zhang Yi-Jian YJ Lu Wei W Wu Wen-Guang WG Shu Yi-Jun YJ Weng Hao H Cao Yang Y Bao Run-Fa RF Liang Hai-Bin HB Wang Zheng Z Zhang Yi-Chi YC Gong Wei W Zheng Lei L Sun Shu-Han SH Liu Ying-Bin YB Liu Ying-Bin YB

EMBO reports 20170908 10

Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis ...[more]

PMID: 28887321

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Project description:Objective:To study the role of LncRNA PTTG3P in colorectal cancer (CRC) and the underlying mechanism. Patients and Methods:The expression level of LncRNA PTTG3P was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC cell lines and tumor tissues from 43 CRC patients, and the correlations between LncRNA PTTG3P expression and the clinicopathological indicators and prognosis of CRC patients were analyzed. Then, a PTTG3P knockdown model in CRC cell lines HCT-8 and HCT-116 was constructed. Finally, the relationship between LncRNA PTTG3P and microRNA-155-5p was explored through luciferase reporter experiments and recovery experiments. Results:qRT-PCR results showed that LncRNA PTTG3P was markedly up-regulated in CRC tumor tissues than that in adjacent tissues. Meanwhile, patients with high LncRNA PTTG3P expression had higher rates of lymph node metastasis and distant metastasis. In addition, cell functional experiments suggested that knocking down PTTG3P markedly reduced the migration abilities of CRC cells. Subsequently, bioinformatics analysis and luciferase reporter gene experiments suggested that LncRNA PTTG3P could directly bind to microRNA-155-5P. Analysis of CRC tissue samples showed that microRNA-155-5P expression was markedly reduced in CRC and was negatively correlated with LncRNA PTTG3P. Finally, the recovery experiments also suggested that there was a mutual regulation between LncRNA PTTG3P and microRNA-155-5P, and silencing microRNA-155-5P can reverse the inhibitory effect of knocking down PTTG3P on the malignant progression of CRC. Conclusion:In summary, LncRNA PTTG3P level was markedly increased in CRC, and was highly correlated to the incidence of lymph node metastasis and distant metastasis in CRC patients. In addition, LncRNA PTTG3P might promote the ability of CRC to invade and migrate by downregulating microRNA-155-5P. Therefore, dissecting the aberrant regulation of LncRNA PTTG3P/microRNA-155-5P may be valuable for early screening, guidance treatment, and recurrence detection of CRC.

Dataset Information

LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis.

Publications

LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis.

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