Comprehensive transcriptomic and co-expression analysis of ABL1 gene and molecularly targeted drugs in hepatocellular carcinoma based on multi-database mining.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Consequently, it is essential to identify biomarkers for treatment response and the prognosis prediction. We investigated whether ABL1 can function as a biomarker or a drug target for HCC. We assessed the ABL1 expression, genetic alterations and patients' survival from LinkedOmics, GEO, TCGA and Human Protein Atlas. We analyzed PPI, GO and KEGG pathways. GSEA was analyzed for functional comparison. The current drugs targeting ABL1 were statistically analyzed using DRUGSURV and DGIdb database. We found ABL1 is overexpressed in HCC and its higher expression reduces survival probability. Genetic changes of ABL1 are not frequent. We screened out 25 differentially expressed genes correlated with ABL1. The top functions of ABL1 are biological regulation, metabolic process, protein-containing, and protein binding. KEGG pathways showed that ABL1 and correlated with ABL1 significantly genes markedly enriched in the ErbB signaling pathway, and pathways in cancer. We counted the existing drugs targeting ABL1, which indicates that inhibiting ABL1 expression may improve the survival probability of HCC. In conclusion, ABL1 plays a crucial role in the development and progression of this cancerization and is a potential drug target.

The multi-molecular mechanisms of tumor-targeted drug resistance in precision medicine.

Clinically, cancer drug therapy is still dominated by chemotherapy drugs. Although the emergence of targeted drugs has greatly improved the survival rate of patients with advanced cancer, drug resistance has always been a difficult problem in clinical cancer treatment. At the current level of medicine, most drugs cannot escape the fate of drug resistance. With the emergence and development of gene detection, liquid biopsy ctDNA technology, and single-cell sequencing technology, the molecular mechanism of tumor drug resistance has gradually emerged. Drugs can also be updated in response to drug resistance mechanisms and bring higher survival benefits. The use of new drugs often leads to new mechanisms of resistance. In this review, the multi-molecular mechanisms of drug resistance are introduced, and the overcoming of drug resistance is discussed from the perspective of the tumor microenvironment.

Cloning and primary immunological study of TGF-ß1 and its receptors TßR I /TßR II in tilapia(Oreochromis niloticus).

The transforming growth factor ß (TGF-ß) superfamily plays critical roles in tumor suppression, cell proliferation and differentiation, tissue morphogenesis, lineage determination, cell migration and apoptosis. Recently, TGF-ß1, one important member of TGF-ß superfamily, is suggested as an immune regulator in the teleost. In this study, we cloned the cDNAs of TGF-ß1 and its receptors, TßR I and TßR II (including three isoforms) from tilapia (Genbank accession numbers: KP754231- KP754235). A tissue distribution profile analysis indicated that TGF-ß1 was highly expressed in the head kidney, gill, spleen, kidney and PBLs (peripheral blood leukocytes); TßR I only showed considerable expression in the liver; and TßR II-2 was highly expressed in the kidney, gill, liver, head kidney and heart. We determined that the mRNA expressions of TGF-ß and TßR I /TßR II-2 were significantly increased in tilapia head kidney and spleen leukocytes by the stimulation of Lipopolysaccharide (LPS) or Poly I: C. We also examined their expressions in the spleen and head kidney of tilapia after IP injection of streptococcus agalactiae. The results showed that the mRNA expressions of these three genes all increased in the head kidney as early as 6 h post infection, and in the spleen 3 d post infection. In addition, the protein level of TGF-ß1 was also up-regulated in the head kidney and the spleen after infection. Taken together, our data indicate that the TGF-ß1-TßR I /TßR II-2 system functions potentially in tilapia immune system.

Molecular cloning, functional identification and expressional analyses of FasL in Tilapia, Oreochromis niloticus.

FasL is the most extensively studied apoptosis ligand. In 2000, tilapia FasL was identified using anti-human FasL monoclonal antibody by Evans's research group. Recently, a tilapia FasL-like protein of smaller molecule weight was predicted in Genbank (XM_003445156.2). Based on several clues drawn from previous studies, we cast doubt on the authenticity of the formerly identified tilapia FasL. Conversely, using reverse transcription polymerase chain reaction (RT-PCR), the existence of the predicted FasL-like was verified at the mRNA level (The Genbank accession number of the FasL mRNA sequence we cloned is KM008610). Through multiple alignments, this FasL-like protein was found to be highly similar to the FasL of the Japanese flounder. Moreover, we artificially expressed the functional region of the predicted protein and later confirmed its apoptosis-inducing activity using a methyl thiazolyl tetrazolium (MTT) assay, Annexin-V/Propidium iodide (PI) double staining, and DNA fragment detection. Supported by these evidences, we suggest that the predicted protein is the authentic tilapia FasL. To advance this research further, tilapia FasL mRNA and its protein across different tissues were quantified. High expression levels were identified in the tilapia immune system and sites where active cell turnover conservatively occurs. In this regard, FasL may assume an active role in the immune system and cell homeostasis maintenance in tilapia, similar to that shown in other species. In addition, because the distribution pattern of FasL mRNA did not synchronize with that of the protein, post-transcriptional expression regulation is suggested. Such regulation may be dominated by potential adenylate- and uridylate-rich elements (AREs) featuring AUUUA repeats found in the 3' untranslated region (UTR) of tilapia FasL mRNA.