Let‑7b binding site polymorphism in the B‑cell lymphoma‑extra large 3'UTR is associated with fluorouracil resistance of hepatocellular carcinoma

  • Authors:
    • Jin Ma
    • Rui Guo
    • Ting Wang
    • Xia Pan
    • Xiaoyong Lei
  • View Affiliations

  • Published online on: October 17, 2014     https://doi.org/10.3892/mmr.2014.2692
  • Pages: 677-681
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

B‑cell lymphoma‑extra large (Bcl‑xl) is an anti‑apoptotic member of the B‑cell lymphoma 2 (Bcl‑2) family that is often found to be overexpressed in human hepatocellular carcinoma (HCC), therefore conferring a survival advantage to tumor cells. microRNA (miRNA) let‑7b is downregulated in HCC and its expression correlates with multidrug resistance. Using computational programs, it was predicted that the 3' untranslated region (UTR) of the Bcl‑xl gene contains a potential miRNA binding site for let‑7b, and that a single nucleotide polymorphism (SNP) site rs3208684 (A or C allele) resides within this binding site. Luciferase assays and western blot analysis demonstrated that let‑7b targeted Bcl‑xl gene expression and negatively regulated the amount of Bcl‑xl protein. SNP rs3208684 (A>C) variation enhanced the expression of Bcl‑xl by disrupting the binding of let‑7b to the 3'UTR of Bcl‑xl. The effects of the two polymorphic variants on chemotherapeutic drug sensitivity were determined by cell counting kit 8 assays. Overexpression of the Bcl‑xl mutated (C) allele in BEL‑7402 HCC cells significantly decreased fluorouracil (5‑FU) sensitivity, as compared with mock transfection and overexpression of the wild‑type allele. From this, it was concluded that let‑7b increased 5‑FU sensitivity by repressing Bcl‑xl expression in HCC cells. These results suggest that SNP (rs3208684) may be a potential marker for personalized treatment.
View Figures
View References

Related Articles

Journal Cover

January-2015
Volume 11 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ma J, Guo R, Wang T, Pan X and Lei X: Let‑7b binding site polymorphism in the B‑cell lymphoma‑extra large 3'UTR is associated with fluorouracil resistance of hepatocellular carcinoma. Mol Med Rep 11: 677-681, 2015
APA
Ma, J., Guo, R., Wang, T., Pan, X., & Lei, X. (2015). Let‑7b binding site polymorphism in the B‑cell lymphoma‑extra large 3'UTR is associated with fluorouracil resistance of hepatocellular carcinoma. Molecular Medicine Reports, 11, 677-681. https://doi.org/10.3892/mmr.2014.2692
MLA
Ma, J., Guo, R., Wang, T., Pan, X., Lei, X."Let‑7b binding site polymorphism in the B‑cell lymphoma‑extra large 3'UTR is associated with fluorouracil resistance of hepatocellular carcinoma". Molecular Medicine Reports 11.1 (2015): 677-681.
Chicago
Ma, J., Guo, R., Wang, T., Pan, X., Lei, X."Let‑7b binding site polymorphism in the B‑cell lymphoma‑extra large 3'UTR is associated with fluorouracil resistance of hepatocellular carcinoma". Molecular Medicine Reports 11, no. 1 (2015): 677-681. https://doi.org/10.3892/mmr.2014.2692