Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma

Кривцова, О. М.; Макарова, А. С.; Лазаревич, Н. Л.

doi:10.4254/wjh.v10.i10.645

Cited by 8 publications

(7 citation statements)

References 147 publications

(210 reference statements)

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“…Changes in expression levels and consequent rewiring are mediated by expression levels of cell type-specific transcription factor isoforms, generated by, e.g., alternative splicing (89), or by different factors. Data support the involvement of transcription factors in rewiring [e.g., (90,91)].…”

Section: Ois and Premature Senescencementioning

confidence: 56%

How can same-gene mutations promote both cancer and developmental disorders?

2022

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Section: Ois and Premature Senescencementioning

confidence: 56%

How can same-gene mutations promote both cancer and developmental disorders?

2022

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“…Aberrant activation of several signaling cascades, such as EGFR-Ras-MAPKK, PI3K/Akt/mTOR, Wnt-β-catenin, Hedgehog signalling, and apoptotic pathways, have been reported in HCC 37. Deregulation of the networks of tissue-specific transcription factors (eg, HNF4α, C/EBPs, p73, and TCF7L2) observed in HCC leads to profound changes in the hepatic transcriptional program that facilitates tumor progression 38. Identifying the important molecules involved in HCC development is of great importance for developing effective therapeutic approaches for HCC.…”

Section: Discussionmentioning

confidence: 99%

<p>miR-1-3p suppresses proliferation of hepatocellular carcinoma through targeting SOX9</p>

Zhang

Gao

et al. 2019

OTT

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BackgroundLiver cancer was the fourth leading cause of cancer-related death in 2015. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. miR-1-3p plays important roles in cancer, including prostate, bladder, lung cancer, and colorectal carcinoma. The function of miR-1-3p in HCC remains poorly understood.MethodsqRT-PCR was performed to detect the miR-1-3p expression in HCC cell lines (HCCLM3, Hep3B, Bel-7404, SMMC-7721) and the normal human hepatic cell line (LO2). HCCLM3 and Bel-7404 cells were transfected with miR-1-3p mimic or scramble control followed by water-soluble tetrazolium salt (WST-1) assay. Western bolt analysis was performed to determine the protein levels. TargetScan7.1 (http://www.targetscan.org/vert_71/) was used to predict the potential targets of miR-1-3p. SRY (sex determining region Y)-box 9 (SOX9), which has been previously shown to play an important role in HCC, was found to be a target of miR-1-3p. Luciferase reporter assay was used to explore the targeting of miR-1-3p on SOX9. For in vivo tumorigenesis assay, HCCLM3 cells with stable overexpression of miR-1-3p or control plasmid were injected subcutaneously into the flank of the SCID mice and animals were monitored for tumor growth.ResultsmiR-1-3p was significantly downregulated in HCC cell lines (HCCLM3, Hep3B, Bel-7404, and SMMC-7721) compared to normal human hepatic cell line (LO2). Overexpression of miR-1-3p significantly inhibited the proliferation and induced apoptosis in HCCLM3 and Bel-7474 cells. SOX9 was a direct target of miR-1-3p in HCC cells. Inhibition of SOX9 significantly inhibited the proliferation of HCCLM3 and Bel-7474 cells. In vivo, overexpression of miR-1-3p decreased tumor volume in a xenograft model.ConclusionThese results highlight the role of miR-1-3p in HCC. Overexpression of miR-1-3P inhibited the proliferation of HCC at least partly due to the regulation of SOX9. miR-1-3p may be a promising therapeutic candidate for HCC.

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“…For example, splice variant 1 (SV1) is a truncated isoform of KLF6 that has no zinc finger domains, yet it promotes tumor migration, and is thought to stimulate EMT in HCC (121). Hepatocyte nuclear factor 4α (HNF4α) has alternative isoforms that both stimulate (HNF4α7, 8, 9) and repress (HNF4α1, 2, 3) cancer development (121)(122)(123). We also cannot rule out the possibility of alternative TF splice isoforms in epithelial and mesenchymal cells.…”

Section: Factoring In Transcriptional Regulation In Emtmentioning

confidence: 99%

Unresolved Complexity in the Gene Regulatory Network Underlying EMT

Lavin

Tiwari

2020

Front. Oncol.

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Epithelial to mesenchymal transition (EMT) is the process whereby a polarized epithelial cell ceases to maintain cell-cell contacts, loses expression of characteristic epithelial cell markers, and acquires mesenchymal cell markers and properties such as motility, contractile ability, and invasiveness. A complex process that occurs during development and many disease states, EMT involves a plethora of transcription factors (TFs) and signaling pathways. Whilst great advances have been made in both our understanding of the progressive cell-fate changes during EMT and the gene regulatory networks that drive this process, there are still gaps in our knowledge. Epigenetic modifications are dynamic, chromatin modifying enzymes are vast and varied, transcription factors are pleiotropic, and signaling pathways are multifaceted and rarely act alone. Therefore, it is of great importance that we decipher and understand each intricate step of the process and how these players at different levels crosstalk with each other to successfully orchestrate EMT. A delicate balance and fine-tuned cooperation of gene regulatory mechanisms is required for EMT to occur successfully, and until we resolve the unknowns in this network, we cannot hope to develop effective therapies against diseases that involve aberrant EMT such as cancer. In this review, we focus on data that challenge these unknown entities underlying EMT, starting with EMT stimuli followed by intracellular signaling through to epigenetic mechanisms and chromatin remodeling.

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Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma

Cited by 8 publications

References 147 publications

How can same-gene mutations promote both cancer and developmental disorders?

How can same-gene mutations promote both cancer and developmental disorders?

<p>miR-1-3p suppresses proliferation of hepatocellular carcinoma through targeting SOX9</p>

Unresolved Complexity in the Gene Regulatory Network Underlying EMT

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