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  2. LncRNA LHFPL3-AS1 contributes to tumorigenesis of melanoma stem cells via the miR-181a-5p/BCL2 pathway

LncRNA LHFPL3-AS1 contributes to tumorigenesis of melanoma stem cells via the miR-181a-5p/BCL2 pathway

  • Cell Death Dis. 2020 Nov 4;11(11):950. doi: 10.1038/s41419-020-03141-1.
Song Zhang 1 Haitao Wan 1 Xiaobo Zhang 2
Affiliations

Affiliations

  • 1 College of Life Sciences and Laboratory for Marine Biology and Biotechnology of Qingdao National Laboratory for Marine Science and Technology, Zhejiang University, Hangzhou, 310058, The People's Republic of China.
  • 2 College of Life Sciences and Laboratory for Marine Biology and Biotechnology of Qingdao National Laboratory for Marine Science and Technology, Zhejiang University, Hangzhou, 310058, The People's Republic of China. zxb0812@zju.edu.cn.
Abstract

Long noncoding RNAs (lncRNAs) are recognized as a new area for Cancer therapy. B-cell lymphoma-2 (Bcl-2)-mediated suppression of Apoptosis is an important molecular hallmark of Cancer. However, the influence of lncRNA on the regulation of oncogenic Bcl-2 in Cancer Stem Cells has not been explored. In this study, our findings revealed that the lncRNA LHFPL3-AS1-long, generated from the polypyrimidine tract binding protein 1 (PTBP1)-mediated splicing of the LHFPL3-AS1 precursor, upregulated BCL2 protein to contribute to tumorigenesis of melanoma stem cells. The in vitro and in vivo results showed that LHFPL3-AS1-long directly interacted with miR-181a-5p to inhibit the mRNA degradation of Bcl-2 (the target of miR-181), thus suppressing Apoptosis of melanoma stem cells. The splicing factor PTBP1 regulated the alternative splicing of LHFPL3-AS1 transcript by preferentially binding to the motifs located in exon3 of LHFPL3-AS1 precursor, leading to the biogenesis of LHFPL3-AS1-long in melanoma stem cells. In patients with melanoma, the expressions of PTBP1 and LHFPL3-AS1 were significantly upregulated compared with the healthy donors. Therefore, our study revealed a mechanistic crosstalk among an onco-splicing factor, lncRNA and tumorigenesis of melanoma stem cells, enabling PTBP1 and LHFPL3-AS1 to serve as the attractive therapeutic targets for melanoma.

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