Kinesin family member 15 promotes cancer stem cell phenotype and malignancy via reactive oxygen species imbalance in hepatocellular carcinoma

Li, Qing; Qiu, Jiannan; Yang, Hui; Sun, Guangli; Hu, Yangbo; Zhang, Deming; Deng, Zhangshuang; Wang, Xuehao; Tang, Jinhai; Jiang, Runqiu

doi:10.1016/j.canlet.2019.11.008

Cited by 53 publications

(41 citation statements)

References 40 publications

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“…Since we found that KIF15 promoted HCC proliferation, KIF15 therefore became a good therapeutic target for HCC because of their role during mitosis. And a new study reported that KIF15 downregulation delayed tumor initiation, growth, and metastasis in vitro and in vivo [36]. Based on the previous data and our results combination, drug therapy targeting both KIF15 could be considered as lead therapies in further drug development for HCC.…”

Section: Analytical Cellular Pathologysupporting

confidence: 69%

KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

Sun

Shi

et al. 2020

Analytical Cellular Pathology

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Liver cancer is thought as the most common human malignancy worldwide, and hepatocellular carcinoma (HCC) accounts for nearly 90% liver cancer. Due to its poor early diagnosis and limited treatment, HCC has therefore become the most lethal malignant cancers in the world. Recently, molecular targeted therapies showed great promise in the treatment of HCC, and novel molecular therapeutic targets is urgently needed. KIF15 is a microtubule-dependent motor protein involved in multiple cell processes, such as cell division. Additionally, KIF15 has been reported to participate in the growth of various types of tumors; however, the relation between KIF15 and HCC is unclear. Herein, our study investigated the possible role of KIF15 on the progression of HCC and found that KIF15 has high expression in tumor samples from HCC patients. KIF15 could play a critical role in the regulation of cell proliferation of HCC, which was proved by in vitro and in vivo assays. In conclusion, this study confirmed that KIF15 could be a novel therapeutic target for the treatment of HCC.

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Section: Analytical Cellular Pathologysupporting

confidence: 69%

KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

Sun

Shi

et al. 2020

Analytical Cellular Pathology

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“…HCC and adjacent non-tumor specimens were obtained from 120 patients who underwent hepatectomy at the Hepatobiliary Center of The First Affiliated Hospital of Nanjing Medical University between February 2013 and December 2019, as previously described. 41 HCC cell lines were purchased from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China) and cultured as per the established protocol. 5 We established YTHDF1-knockout SMMC7721 cells using the CRISPR-Cas9 genome editing system and generated stable YTHDF1 knockdown Huh7 cells.…”

Section: Methodsmentioning

confidence: 99%

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

Zhang

et al. 2021

Sig Transduct Target Ther

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N6-methyladenosine (m6A), and its reader protein YTHDF1, play a pivotal role in human tumorigenesis by affecting nearly every stage of RNA metabolism. Autophagy activation is one of the ways by which cancer cells survive hypoxia. However, the possible involvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma (HCC). In this study, specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing, -knockout, and -knockdown HCC cells, HCC organoids, and HCC patient-derived xenograft (PDX) murine models. YTHDF1 expression and hypoxia-induced autophagy were significantly correlated in vitro; significant overexpression of YTHDF1 in HCC tissues was associated with poor prognosis. Multivariate cox regression analysis identified YTHDF1 expression as an independent prognostic factor in patients with HCC. Multiple HCC models confirmed that YTHDF1 deficiency inhibited HCC autophagy, growth, and metastasis. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region under hypoxia. The results of methylated RNA immunoprecipitation sequencing, proteomics, and polysome profiling indicated that YTHDF1 contributed to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modified ATG2A and ATG14 mRNA, thus facilitating autophagy and autophagy-related malignancy of HCC. Taken together, HIF-1α-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner. Our findings suggest that YTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.

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“…Further mechanistic research showed that KIF15 markedly decreased intracellular ROS levels and increased the LCSC phenotype via phosphoglycerate dehydrogenase (PHGDH). Furthermore, the chromatin-associated protein ANCCA (also known as ATAD2, the ATPase family AAA domain-containing protein 2) appears to have an important role in enhancing KIF15 expression (Li Q. et al, 2019).…”

Section: Kif15mentioning

confidence: 99%

Recent Advances in Liver Cancer Stem Cells: Non-coding RNAs, Oncogenes and Oncoproteins

Zhu

2020

Front. Cell Dev. Biol.

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Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide, with high morbidity, relapse, metastasis and mortality rates. Although liver surgical resection, transplantation, chemotherapy, radiotherapy and some molecular targeted therapeutics may prolong the survival of HCC patients to a certain degree, the curative effect is still poor, primarily because of tumor recurrence and the drug resistance of HCC cells. Liver cancer stem cells (LCSCs), also known as liver tumor-initiating cells, represent one small subset of cancer cells that are responsible for disease recurrence, drug resistance and death. Therefore, understanding the regulatory mechanism of LCSCs in HCC is of vital importance. Thus, new studies that present gene regulation strategies to control LCSC differentiation and replication are under development. In this review, we provide an update on the latest advances in experimental studies on non-coding RNAs (ncRNAs), oncogenes and oncoproteins. All the articles addressed the crosstalk between different ncRNAs, oncogenes and oncoproteins, as well as their upstream and downstream products targeting LCSCs. In this review, we summarize three pathways, the Wnt/β-catenin signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, and interleukin 6/Janus kinase 2/signal transducer and activator of transcription 3 (IL6/JAK2/STAT3) signaling pathway, and their targeting gene, c-Myc. Furthermore, we conclude that octamer 4 (OCT4) and Nanog are two important functional genes that play a pivotal role in LCSC regulation and HCC prognosis.

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Kinesin family member 15 promotes cancer stem cell phenotype and malignancy via reactive oxygen species imbalance in hepatocellular carcinoma

Cited by 53 publications

References 40 publications

KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

Recent Advances in Liver Cancer Stem Cells: Non-coding RNAs, Oncogenes and Oncoproteins

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