Homoharringtonine inhibited breast cancer cells growth via miR-18a-3p/AKT/mTOR signaling pathway

Wang, Libin; Wang, Danni; Wu, Ligang; Cao, Jia; Tian, Jinhai; Liu, Rong; Ma, Rong; Yu, Jingjing; Wang, Jia; Huang, Qi; Xiong, Wenyong; Zhang, Xu

doi:10.7150/ijbs.44907

Cited by 29 publications

(17 citation statements)

References 25 publications

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“…In H. pylori -associated gastric cancer, miR-18a-3p was increased and upregulating miR-18a-3p stimulated the growth and motility of gastric cancer cell lines in vitro ( Tsai et al, 2020 ). In addition, miR-18a-3p played a critical role in the inhibitory effect of homoharringtonine on breast cancer via targeting the AKT-mTOR pathway, and miR-18a-3p inhibitor facilitated HHT-induced cancer cell apoptosis ( Wang LB. et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA

Luo

Tao

et al. 2022

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and its incidence is still high in China. This study aimed to investigate the circular RNAs (circRNAs) involved in the development of HCC and elucidate the mechanism. RNA sequencing found 72 downregulated circRNAs and 88 upregulated circRNAs in human HCC tissues, including hsa_circ_0098181, hsa_circ_0072309, hsa_circ_0000831, and hsa_circ_0000231. The reduction of hsa_circ_0098181 was confirmed in eight paired human HCC tissues, hepatoma cell lines, and CCL4/DEN-induced mouse HCC models by RT-qPCR. The FISH assay revealed that hsa_circ_0098181 is mainly located in the cytoplasm of hepatocytes in the paratumor tissues. Further log-rank analysis performed in 91 HCC patients demonstrated that low expression of hsa_circ_0098181 was related to poor prognosis. The plasmid and lentivirus overexpressing hsa_circ_0098181 were delivered into HCC cell lines. After hsa_circ_0098181 was upregulated, the proliferation, invasion, migration, and colony formation of HCC cell lines were inhibited, and the apoptosis was promoted. Moreover, exogenous hsa_circ_0098181 delivery mitigated the tumor formation ability of Huh7 in Balb/C nude mice. The dual-luciferase reporter assay and the RIP assay verified that hsa_circ_0098181 sponged miR-18a-3p to regulate PPARA. In addition, a rescue experiment found miR-18a-3p mimic partly reversed the suppression of hsa_circ_0098181 on proliferation, invasion, and migration of HCC cell lines. In conclusion, hsa_circ_0098181 can repress the development of HCC through sponging miR-18a-3p and promoting the expression of PPARA in vitro and in vivo, and hsa_circ_0098181 might be a therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA

Luo

Tao

et al. 2022

Front. Pharmacol.

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“…mTOR-related signaling pathways regulates many important biological functions such as cell growth, metabolism, autophagy, homeostasis, protein synthesis, and immune response by forming two important complexes, mTORC1 and mTORC2 . The pathological relevance of mTOR signaling has been demonstrated in human cancers including breast, colon, and skin cancers. − High mTOR expression or p-mTOR level was positively correlated with the degree of malignancy, depth of invasion, lymph node metastasis, and other adverse conditions of esophageal squamous cell carcinoma . In addition, the p-mTOR level also was associated with tumor metastasis and bad prognosis in patients with lung cancer after surgical resection .…”

Section: Mtor and Cancersmentioning

confidence: 99%

Targeting mTOR Signaling by Dietary Polysaccharides in Cancer Prevention: Advances and Challenges

Guo

et al. 2022

J. Agric. Food Chem.

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Cancer is the most serious problem for public health. Traditional treatments often come with unavoidable side effects. Therefore, the therapeutic effects of natural products with wide sources and low toxicity are attracting more and more attention. Polysaccharides have been shown to have cancer-fighting potential, but the molecular mechanisms remain unclear. The mammalian target of rapamycin (mTOR) pathway has become an attractive target of antitumor therapy research in recent years. The regulation of mTOR pathway not only affects cell proliferation and growth but also has an important effect in tumor metabolism. Recent studies indicate that dietary polysaccharides play a vital role in cancer prevention and treatment by regulating mTOR pathway. Here, the progress in targeting mTOR signaling by dietary polysaccharides in cancer prevention and their molecular mechanisms are systemically summarized. It will promote the understanding of the anticancer effects of polysaccharides and provide reference to investigators of this cutting edge field.

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“…Our previous research found that HHT suppressed breast cancer cells growth and promoted apoptosis through miR-18a-3p-AKT-mTOR signaling pathway [11]. Besides, Shi et al [12] found that HHT could decrease LoVo cell growth by inhibiting EphB4 and its downstream signaling.…”

Section: Introductionmentioning

confidence: 99%

NKD1 targeting PCM1 regulates the therapeutic sensitivity of HHT on colorectal cancer cells

Cao

Wang

et al. 2023

Preprint

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Colorectal cancer (CRC) is the most common primary malignant tumor with a significantly higher incidence in the worldwide. Homoharringtonine (HHT) often used to treatment of acute leukemia. Recent research revealed it could be used for solid cancer therapy. However, the regulatory target and mechanism of HHT in CRC progression remain elusive. This study proved that HHT suppressed cell proliferation and promoted cell cycle arrest and apoptosis. Transcriptome sequence indicated that NKD1 was the target of HHT in CRC. HHT could suppress NKD1 expression in a concentration and time dependent manner. NKD1 was overexpressed in CRC tissues and depletion of NKD1 enhanced the therapeutic effect of HHT on CRC in vitro and vivo. Furthermore, proteomic analysis revealed that PCM1 involved in the process of cell proliferation and cell cycle regulated by NKD1. NKD1 interacts with PCM1, and NKD1 promotes the ubiquitination degradation of PCM1. Moreover, overexpression of PCM1 can effectively reverse the promoting effect of NKD1 interference on cell cycle arrest and apoptosis. These results suggested that the NKD1/PCM1 axis participated in mediating the therapeutic sensitivity of HHT to CRC. Our findings provide evidence for clinical application of NKD1-targeted therapy in improving HHT sensitivity for CRC treatment.

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Homoharringtonine inhibited breast cancer cells growth via miR-18a-3p/AKT/mTOR signaling pathway

Cited by 29 publications

References 25 publications

Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA

Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA

Targeting mTOR Signaling by Dietary Polysaccharides in Cancer Prevention: Advances and Challenges

NKD1 targeting PCM1 regulates the therapeutic sensitivity of HHT on colorectal cancer cells

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