Glabridin is a prenylated isoflavan from the roots of Glycyrrhiza glabra Linne and has posed great impact on the areas of drug development and medicine, due to various biological properties such as anti-inflammation, anti-oxidation, anti-tumor, anti-microorganism, bone protection, cardiovascular protection, neuroprotection, hepatoprotection, anti-obesity, and anti-diabetes. Many signaling pathways, including NF-κB, MAPK, Wnt/β-catenin, ERα/SRC-1, PI3K/AKT, and AMPK, have been implicated in the regulatory activities of glabridin. Interestingly, glabridin has been considered as an inhibitor of tyrosinase, P-glycoprotein (P-gp), and CYP2E1 and an activator of peroxisome proliferator-activated receptor γ (PPARγ), although their molecular regulating mechanisms still need further investigation. However, poor water solubility and low bioavailability have greatly limited the clinical applications of glabridin. Hopefully, several effective strategies, such as nanoemulsions, microneedles, and smartPearls formulation, have been developed for improvement.

Triple-negative breast cancers (TNBC) frequently harbor defects in DNA double-strand break repair through homologous recombination (HR), such as BRCA1 dysfunction. However, less than 15% of TNBC patients were found to carry BRCA1 mutation, indicating that there are other mechanisms regulating BRCA1-deficient in TNBC. In the current study, we shown that overexpression of TRIM47 correlates with progression and poor prognosis in triple-negative breast cancer. Moreover, we demonstrated that TRIM47 directly interacts with BRCA1 and induces ubiquitin-ligase-mediated proteasome turnover of BRCA1, subsequently leads to a decrease of BRCA1 protein levels in TNBC. Moreover, the downstream gene expression of BRCA1, such as p53, p27, p21 was significantly reduced in the overexpression of TRIM47 cell lines but increased in TRIM47-deleted cells. Functionally, we found that overexpression of TRIM47 in TNBC cells confers an exquisite sensitivity to olaparib, an inhibitor of poly-(ADP-ribose)-polymerase (PARP), but TRIM47 inhibition significantly confers TNBC cells resistance to olaparib both in vitro and in vivo. Furthermore, we showed that overexpression of BRCA1 significant increase the olaparib resistance in TRIM47-overexpression-induced PARP inhibitions sensitivity. Taken together, our results uncover a novel mechanism for BRCA1-deficient in TNBC and targeting TRIM47/BRCA1 axis may be a promising prognostic factor and a valuable therapeutic target for TNBC.

Sorafenib is the important first-standard drug for patients with advanced hepatocellular carcinoma (HCC). A major obstacle to successful treatment is sorafenib resistance. However, the mechanism of sorafenib resistance is unclear. The present study aimed to determine the involvement of dipeptidyl peptidase-8 (DPP8) in sorafenib resistance. DPP8 expression was detected using quantitative real-time PCR (qPCR) and western blot analysis. The effect of DPP8 on sorafenib resistance was examined using terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL), colony formation, flow cytometry, luciferase reporter, immunofluorescence, and immunoprecipitation (IP) assays. We found that DPP8 mRNA and protein levels were dramatically upregulated in HCC. Gene set enrichment analysis (GSEA) illustrated that DPP8 might be involved in apoptosis regulation. Downregulation of DPP8 substantially promoted the sensitivity of HCC cells to sorafenib. Further analysis showed that DPP8 might regulate nuclear factor kappa B (NF-κB) signaling, which was confirmed using a luciferase reporter assay. Downregulation of DPP8 decreased the expression levels of downstream genes of the NF-κB pathway. IP showed that DPP8 can interact with NF-κB subunit c-Rel, an important protein of NF-κB signaling. Finally, a drug combination of sorafenib and Val-boroPro induced higher mortality of HCC cells than sorafenib alone in DPP8-upregulated cells. Our findings indicated that using the inhibitor Val-boroPro might be a promising method to enhance sorafenib sensitivity in advanced HCC.

Cholangiocarcinoma (CCA) is a type of cancer with a relatively low morbidity, but poor prognosis. Aberrant long non-coding RNA (lncRNA) expression has been observed in the pathological development of CCA. In the present study, lncRNA long intergenic non-protein coding RNA 630 (LINC00630) was found to be significantly upregulated in CCA tissues and cultured cells. LINC00630 expression was positively associated with histological differentiation, TNM stage and lymph node invasion. Short hairpin RNA (sh)-LINC00630 transfection could effectively decrease CCA cell proliferation, migration and invasion. Further investigations found that LINC00630 could interact with microRNA (miR)-199a, which specifically targeted fibroblast growth factor 7 (FGF7) for degradation. FGF7 overexpression restored the sh-LINC00630 transfection-induced decrease in CCA cell proliferation, migration and invasion. In conclusion, LINC00630 significantly promoted CCA cell proliferation, migration and invasion by upregulating FGF7 through miR-199a sponging.

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Hepatocellular carcinoma (HCC) is a lethal malignancy whereas the molecular mechanisms remain poorly understood. Recently, long noncoding RNAs (lncRNA) have been shown to regulate HCC progression. However, the involved lncRNAs remain to be fully explored. Here, we showed the expression pattern and biological function of a recently identified lncRNA, LINC02273, in HCC. LINC02273 played a critical role in HCC progression via stabilizing β-catenin. Knockdown of LINC02237 remarkably inhibited the proliferation, stemness, migration, and invasion abilities, whereas it increased the apoptosis of HCC cells. Overall, we characterized the functions of LINC02273 in HCC and its potential as a novel HCC targeting candidate.

Background Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC. Methods The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells. Results We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC. Conclusions Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance.

Pancreatic cancer remains a deadly solid tumor with worst survival, and a better understanding of the mechanisms of carcinogenesis of pancreatic cancer is critical to promote the survival of patients with pancreatic cancer. qPCR and western blot assay were used to determine the expression of SPRR3 in pancreatic cancer. Anchorage-independent growth ability, BrdU labeling, Transwell assay, and in vivo experiment were used to examine the functions of SPRR3 in aggressiveness of pancreatic cancer. Luciferase reporter assay, nucleoplasmic-separation technique, qPCR, and western blot assay were used to investigate the mechanism of SPRR3 regulating aggressiveness of pancreatic cancer. Our results showed that SPRR3 was significantly increased in pancreatic cancer, which resulted in poor survival for patients with pancreatic cancer. Further analysis showed that overexpression of SPRR3 contributed to anchorage-independent growth ability, growth rate, and invasion ability of pancreatic cancer cells. While, knockdown of SPRR3 showed the reverse results. Mechanistically, overexpression of SPRR3 can promote the transcription of NF-κB pathway, nuclear accumulation of p65, and mRNA levels of NF-κB pathway downstream genes. But, knockdown of SPRR3 induced the reverse results. The above findings clarified the important roles of SPRR3 in the progression of pancreatic cancer through NF-κB pathway. And targeting SPRR3 might be an effective strategy to therapy pancreatic cancer.