The present study aimed to investigate the effects of melatonin (MLT) and 5‑fluorouracil (5‑FU) combination on the chemotherapeutic effect of 5‑FU in esophageal cancer, and determine the potential molecular mechanisms. The effects of MLT and 5‑FU combination on cell proliferation, cell migration and invasion, and cell apoptosis were detected by Cell Counting Kit‑8, Transwell assays and flow cytometric analysis, respectively. Quantitative PCR and western blotting were performed for mRNA and protein quantification, respectively. The present study revealed that MLT significantly inhibited cell activity in a dose‑dependent manner and MLT significantly enhanced 5‑FU‑mediated inhibition of cell proliferation in esophageal cancer cells. Compared with the 5‑FU group, the MLT and 5‑FU combination group significantly inhibited the invasion and migration of EC‑9706 and EC‑109 cells. The present study also revealed that MLT and 5‑FU synergistically promoted apoptosis via activation of the caspase‑dependent apoptosis pathway. Histone-lysine N‑methyltransferase EZH2 (EZH2) was highly expressed in esophageal cancer tissues and cells and its high expression promoted esophageal cancer progression. MLT and 5‑FU combination inhibited cell proliferation and promoted apoptosis by regulating EZH2 expression. In conclusion, MLT enhanced 5‑FU‑mediated inhibition of cell proliferation via promotion of apoptosis by regulating EZH2 expression in esophageal cancer.

Background: The long non-coding RNA (lncRNA) SNHG6 was significantly upregulated in esophageal squamous-cell carcinoma (ESCC), and it promoted ESCC cell proliferation, invasion, and migration. However, the effects of SNHG6 on cell apoptosis and the corresponding underlying mechanisms have not yet reported. Methods: Apoptosis was detected by flow cytometric analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used for mRNA and protein quantification, respectively. A luciferase reporter assay was performed to verify downstream target genes for SNHG6 and miR-101-3p. Results: Dysregulation of SNHG6 inhibited apoptosis in ESCC cells and regulated the expression of apoptosis-related proteins such as Bcl-2, Mcl-1, Bax and Caspase-3. Functionally, miR-101-3p could compete binding with 3′-untranslated region of SNHG6 and downregulation of miR-101-3p reversed its effect on cell apoptosis in SNHG6 knockdown cells. EZH2 was confirmed as a downstream target gene of miR-101-3p, silencing EZH2 expression had the same effect on apoptosis and protein expression as knocking down SNHG6. Overexpression of EZH2 reversed the effects of miR-101-3p overexpression on cell apoptosis in ESCC cells. Conclusion: In this study, we found that upregulation of the lncRNA SNHG6 inhibited apoptosis via miR-101-3p/EZH2 axis in ESCC. These findings may contribute to the diagnosis and treatment of ESCC.

The present study aimed to investigate the influence of circular RNA nuclear receptor‑interacting protein 1 (circNRIP1) on the chemotherapeutic effect of 5‑fluorouracil (5‑FU) in colorectal cancer (CRC) and reveal its potential molecular mechanisms. The effects of circNRIP1 on cell proliferation, migration and invasion, and apoptosis were evaluated using Cell Counting Kit‑8, Transwell and flow cytometric assays, respectively. A dual‑luciferase reporter assay was performed to verify the potential interaction between circNRIP1 and microRNA (miR)‑532‑3p. The results of the present study indicated that circNRIP1 was upregulated in CRC and its increased expression was associated with CRC progression. Furthermore, overexpression of circNRIP1 promoted CRC cell proliferation, invasion and migration, while it inhibited apoptosis. Knockdown of circNRIP1 significantly enhanced the 5‑FU‑induced inhibition of the viability of HCT116 and SW480 cells. Bioinformatics analysis predicted that miR‑532‑3p was a direct target of circNRIP1, which was further confirmed by a dual‑luciferase reporter assay. miR‑532‑3p silencing reversed the effects of circNRIP1 knockdown on the sensitivity of 5‑FU in the chemotherapy of CRC. The results suggested that circNRIP1 and miR‑532‑3p may be utilized to improve the diagnosis of CRC and serve as diagnostic markers. In conclusion, overexpression of circNRIP1 promoted the progression of CRC, while circNRIP1 silencing sensitized CRC cells to 5‑FU via sponging miR‑532‑3p.

Chemotherapy was the main treatment method for esophageal cancer (EC) patients. However, chemotherapy resistance due to multiple factors is a major barrier to EC treatment. For investigating how small nucleolar RNA host gene 6 (SNHG6) affected the 5-fluorouracil (5-FU) resistance in EC as well as its possible molecular mechanism. This work conducted cell viability assay, clone formation, scratch assays together with cell apoptosis for evaluating the roles of SNHG6 and enhancer of zeste homolog 2 (EZH2, the histone-lysine N-methyltransferase). Relevant molecular mechanism was identified by RT-qPCR analysis together with Western-blot (WB) assays. Our data showed that SNHG6 expression increased in EC cells. SNHG6 promotes colony formation and migration, whereas suppresses EC cell apoptosis. SNHG6 silencing markedly promoted 5-FU-mediated suppression on KYSE150 and KYSE450 cells. Additional mechanism studies showed that SNHG6 modulating STAT3 and H3K27me3 via promoting EZH2 level. Similar to the function of SNHG6, abnormal expression of EZH2 promotes the malignancy of EC and intensifies its resistance to 5-FU. In addition, overexpression of EZH2 abolished the role of SNHG6 silencing in 5-FU sensitivity in EC cells. SNHG6 overexpression promoted malignancy of EC and increased EC cell resistance to 5-FU. Besides, further molecular mechanism studies provided a novel regulatory pathways that SNHG6 knockdown promoted EC cell sensitivity to 5-FU by modulating STAT3 and H3K27me3 via promoting EZH2 expression.

Vitamins are vital to sustain normal physiological function, metabolism, and growth for all living organisms. Being an integral component of coenzyme, vitamins can affect the catalytic activities of many enzymes and the expression of drug transporters. Genetic variations in metabolism and/or transporter genes of drugs can influence the exposure of the human body to drugs and/or their active metabolites, thus contributing to the variations in drug responses and toxicities. Nonetheless, pharmacogenomics studies on nutrients have been rarely summarized. In this article, we reviewed recent progress on vitamin pharmacogenomics, for a better understanding on the influence of vitamin-related gene polymorphisms on inter-individual differences in diseases and drug efficacy and safety.