A selective Aurora-A 5′-UTR siRNA inhibits tumor growth and metastasis

Lai, Chin‐Feng; Chen, Ruo Yu; Hsieh, Hsing Pang; Tsai, Shaw-Jenq; Chang, Kung Chao; Yen, Chia Jui; Huang, Yu Chuan; Liu, Yaowen; Lee, Jenq Chang; Lai, Yi Chien; Hung, Liang‐Yi; Lin, Bo

doi:10.1016/j.canlet.2019.12.031

Cited by 13 publications

(7 citation statements)

References 35 publications

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“…Moreover, clinical trials of these KIs as single agents failed to meet therapeutic expectations, with marginal clinical efficacies in both hematologic malignancies and solid cancers ( 46 ). Consequently, short interfering RNAs (siRNA) targeting Aurora A and PLK1, respectively, have been proposed as alternative treatment options with enhanced selectivity and reduced side effects ( 47 – 50 ). Considering these observations, chemically modified or nanoparticle-formulated siRNA or aptamer designed to target CEP192 may be potential therapeutic strategies for tumors, especially for HCC.…”

Section: Discussionmentioning

confidence: 99%

CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma

Liang

Chang

et al. 2022

Front. Immunol.

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Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand–receptor axes, including IL11–IL11RA, IL6–IL6R, and IL13–IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC.

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Section: Discussionmentioning

confidence: 99%

CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma

Liang

Chang

et al. 2022

Front. Immunol.

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“…107 , 108 In clinical trials, its selective inhibitors or siRNA have been demonstrated to have anti-tumor effects. 109 , 110 Mechanically, MALAT1 upregulated the expression of Aurora-A by sponging miR-140-5p to intensify sorafenib resistance of HCC cells. Clinical patient tissue tests further confirmed these results.…”

Section: Correlation Between Lncrnas and Anti-angiogenic Therapy Resi...mentioning

confidence: 99%

The role of long non-coding RNAs in angiogenesis and anti-angiogenic therapy resistance in cancer

Liu

Zhang

Yang

et al. 2022

Molecular Therapy - Nucleic Acids

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“… Preclinical Cell level [ 120 ] SSO(locked nucleic acid, LNA) Aurora-A Target exon 2-containing Aurora-A 5’-UTR SSO targets the carcinogenic exon 2-containing Aurora-A mRNA isoforms can inhibit tumor growth. Preclinical Cell level Mice level [ 136 ] SSO (antisense morpholino oligomer) VEGFR Against 5’SS of exon13-intron13 junction SSO is directed against the junction sequence that shifts expression from mVEGFR2 to the antiangiogenic sVEGFR. Preclinical Cell level [ 91 ] 10058-F4(MYC inhibitor) ITGA6 MYC inhibitor MYC inhibitor increases the epithelial splicing regulatory protein 2 (ESRP2) and decreases the tumor promoter ITGA6a variant.…”

Section: Potential Tumor Diagnosis and Treatment Targets For Crcmentioning

confidence: 99%

Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment

et al. 2021

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Alternative splicing (AS) is an important event that contributes to posttranscriptional gene regulation. This process leads to several mature transcript variants with diverse physiological functions. Indeed, disruption of various aspects of this multistep process, such as cis- or trans- factor alteration, promotes the progression of colorectal cancer. Therefore, targeting some specific processes of AS may be an effective therapeutic strategy for treating cancer. Here, we provide an overview of the AS events related to colorectal cancer based on research done in the past 5 years. We focus on the mechanisms and functions of variant products of AS that are relevant to malignant hallmarks, with an emphasis on variants with clinical significance. In addition, novel strategies for exploiting the therapeutic value of AS events are discussed.

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A selective Aurora-A 5′-UTR siRNA inhibits tumor growth and metastasis

Cited by 13 publications

References 35 publications

CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma

CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma

The role of long non-coding RNAs in angiogenesis and anti-angiogenic therapy resistance in cancer

Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment

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