Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 2, Pages 1572-1580Publisher
WILEY
DOI: 10.1111/jcmm.14068
Keywords
competing endogenous RNA; hepatic stellate cell; HOTTIP; miR-150
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Funding
- National Natural Science Foundation of China [81500458/H0317, 81873576/H0317, 81000176/H0317]
- Zhejiang Provincial Natural Science Foundation of China [LY16H030012]
- Shanghai Municipal Natural Science Foundation [17ZR1426100]
- Wenzhou Municipal Science and Technology Bureau [Y20150091]
- Key Project of the Science & Technology Development Fund of Nanjing Medical University [2016NJMUZD092]
- Science & Technology Commission of Shanghai Songjiang [16SJGG38]
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HOXA transcript at the distal tip (HOTTIP) has been shown to be up-regulated in a variety of cancers and is identified as an oncogenic long noncoding RNA. However, the biological role of HOTTIP in liver fibrosis is unclear. Here, we reported that HOTTIP was specifically overexpressed in activated hepatic stellate cells (HSCs). HOTTIP knockdown suppressed the activation and proliferation of HSCs. Luciferase reporter assay showed that HOTTIP and serum response factor (SRF) were targets of miR-150. RNA binding protein immunoprecipitation assay indicated the interaction between miR-150 and HOTTIP. Further study revealed that HOTTIP increased SRF expression as a competing endogenous RNA for miR-150, thus prompting HSC activation. Taken together, we provide a novel HOTTIP-miR-150-SRF signalling cascade in liver fibrosis.
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