circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1

Lin, Shuwen; Lin, Ye; Wu, Zhongshi; Xia, Wuzheng; Miao, Chenglong; Peng, Tianyi; Zhao, Zhen; Ji, Chenggang; Mo, Zhikang; Liu, Xi; Jian, Zhixiang

doi:10.3389/fonc.2021.724415

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…circRNAs retained in the cytoplasm act as miRNA sponges to regulate the expression of miRNA target genes (51). Lin et al (52) showed that circRPS16 acts as a miR-876-5p sponge to regulate the expression of SPINK1 in HCC. In HCC, miR-876-5p acts as the target of lncRNA PITPNA-AS1, long noncoding RNA SNHG14 and LINC-ROR, thereby regulating HCC proliferation and sorafenib sensitivity (53).…”

Section: Spink1 Is Regulated By Mirnamentioning

confidence: 99%

SPINKs in Tumors: Potential Therapeutic Targets

Liao

Wang

et al. 2022

Front. Oncol.

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The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.

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Section: Spink1 Is Regulated By Mirnamentioning

confidence: 99%

SPINKs in Tumors: Potential Therapeutic Targets

Liao

Wang

et al. 2022

Front. Oncol.

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“…( Ueno et al, 2014;Shibasaki et al, 2015) SPINK1 Promoting HCC cell proliferation, cell cycle, and invasion in vitro (Huang et al, 2021;Lin et al, 2021) Downregulating E-cadherin and inducing EMT of HCC to promote metastasis Ying et al (2017) It could be regarded as a potential biomarker for early detection and targeted therapy of HCC. (Marshall et al, 2013;Li et al, 2015;Jia et al, 2022) It was a downstream effector of the CDH17/β-catenin axis in HCC.…”

Section: Mt1mmentioning

confidence: 99%

A novel diagnostic four-gene signature for hepatocellular carcinoma based on artificial neural network: Development, validation, and drug screening

Chen

Xie

et al. 2022

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) is one of the most common cancers with high mortality in the world. HCC screening and diagnostic models are becoming effective strategies to reduce mortality and improve the overall survival (OS) of patients. Here, we expected to establish an effective novel diagnostic model based on new genes and explore potential drugs for HCC therapy.Methods: The gene expression data of HCC and normal samples (GSE14811, GSE60502, GSE84402, GSE101685, GSE102079, GSE113996, and GSE45436) were downloaded from the Gene Expression Omnibus (GEO) dataset. Bioinformatics analysis was performed to distinguish two differentially expressed genes (DEGs), diagnostic candidate genes, and functional enrichment pathways. QRT-PCR was used to validate the expression of diagnostic candidate genes. A diagnostic model based on candidate genes was established by an artificial neural network (ANN). Drug sensitivity analysis was used to explore potential drugs for HCC. CCK-8 assay was used to detect the viability of HepG2 under various presentative chemotherapy drugs.Results: There were 82 DEGs in cancer tissues compared to normal tissue. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and infiltrating immune cell analysis were administered and analyzed. Diagnostic-related genes of MT1M, SPINK1, AKR1B10, and SLCO1B3 were selected from DEGs and used to construct a diagnostic model. The receiver operating characteristic (ROC) curves were 0.910 and 0.953 in the training and testing cohorts, respectively. Potential drugs, including vemurafenib, LOXO-101, dabrafenib, selumetinib, Arry-162, and NMS-E628, were found as well. Vemurafenib, dabrafenib, and selumetinib were observed to significantly affect HepG2 cell viability.Conclusion: The diagnostic model based on the four diagnostic-related genes by the ANN could provide predictive significance for diagnosis of HCC patients, which would be worthy of clinical application. Also, potential chemotherapy drugs might be effective for HCC therapy.

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SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma

Man,

Zhou,

et al. 2023

Nat Commun

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Tumor lineage plasticity, considered a hallmark of cancer, denotes the phenomenon in which tumor cells co-opt developmental pathways to attain cellular plasticity, enabling them to evade targeted therapeutic interventions. However, the underlying molecular events remain largely elusive. Our recent study identified CD133/Prom1 in hepatocellular carcinoma (HCC) tumors to mark proliferative tumor-propagating cells with cancer stem cell-like properties, that follow a dedifferentiation trajectory towards a more embryonic state. Here we show SPINK1 to strongly associate with CD133 + HCC, and tumor dedifferentiation. Enhanced transcriptional activity of SPINK1 is mediated by promoter binding of ELF3, which like CD133, is found to increase following 5-FU and cisplatin treatment; while targeted depletion of CD133 will reduce both ELF3 and SPINK1. Functionally, SPINK1 overexpression promotes tumor initiation, self-renewal, and chemoresistance by driving a deregulated EGFR-ERK-CDK4/6-E2F2 signaling axis to induce dedifferentiation of HCC cells into their ancestral lineages. Depleting SPINK1 function by neutralizing antibody treatment or in vivo lentivirus-mediated Spink1 knockdown dampens HCC cancer growth and their ability to resist chemotherapy. Targeting oncofetal SPINK1 may represent a promising therapeutic option for HCC treatment.

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circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1

Cited by 3 publications

References 40 publications

SPINKs in Tumors: Potential Therapeutic Targets

SPINKs in Tumors: Potential Therapeutic Targets

A novel diagnostic four-gene signature for hepatocellular carcinoma based on artificial neural network: Development, validation, and drug screening

SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma

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