4.7 Article

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

Journal

EMBO REPORTS
Volume 18, Issue 10, Pages 1837-1853

Publisher

WILEY
DOI: 10.15252/embr.201744147

Keywords

ceRNA; gallbladder cancer; lncRNA; PAGBC; prognosis

Funding

  1. National Natural Science Foundation of China [81502433, 31620103910, 91440203]
  2. Program for Changjiang Scholars
  3. Leading Talent Program of Shanghai
  4. Shanghai RisingStar Program [15QA1403100]
  5. Shanghai Science and Technology Commission Key Basic Research Program [16JC1400200]
  6. Key Program of Shanghai Science and Technology Commission [16411952501]
  7. Multiple Central Clinical Research Program of Shanghai Jiao Tong University School of Medicine [DLY201507]
  8. Precision Medicine Research Program of Shanghai Jiao Tong University School of Medicine [15ZH4003]
  9. Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine [BXJ201426]
  10. Hangzhou Science and Technology Commission Project [20140633B04]

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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.

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