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Post translational modifications (PTMs) can change the properties of a protein by covalent addition of functional groups to one or more amino acids, and influence almost all aspects of normal cell biology and pathogenesis. Lactylation is a novel identified PTM, and has been found in both histone and non-histone proteins. Since associated with the end product of glycolysis-- lactate, lactylation modification could provide a new perspective for understanding the relationship between metabolic reprogramming and epigenetic modifications. Accumulated evidences suggest that lactylation play important roles in tumor progression and links to poor prognosis in clinical studies. Histone lactylation can affect gene expression in tumor cells and immunological cells, further promoting tumor progression and immune suppression. Lactylation on non-histone proteins can also regulate tumor progression and drug resistance. In this review, we aimed to summarize the roles of lactylation in cancer progression, microenvironment interactions and immune suppression, try to identify new molecular targets for cancer therapy and provide a new direction for combined targeted therapy and immunotherapy.

The occurence and development of tumors is a complicated process, which not only depends on the mutation or deletion of genes, but also is affected by epigenetic regulation. Accumulating evidences have shown that epigenetic modifications play fundamental roles in transcriptional regulation, heterochromatin formation, X chromosome inactivation, DNA damage response and tumor development. SET domain containing lysine methyltransferase 7 (SETD7) was initially identified as an important lysine methyltransferase, which methylated histone and non-histone proteins. These modifications play fundamental roles. Once this modification disorders, it can directly lead to cell abnormalities and cause many diseases. Studies have shown that SETD7 is related to the occurence and development of various tumors, but the methylation sites of SETD7 and its regulatory mechanism have not been fully elucidated. This article summarizes the research progress of the role of SETD7 on histone and non-histone methylation modification in tumors and the molecular mechanism, in order to provide new therapeutic targets for tumor pathogenesis and diagnosis.

MicroRNAs are a class of small noncoding RNAs (20-22 nucleotides). MicroRNAs regulate gene expression by directly binding gene’s 3’-UTR regions. Many studies reveal that miRNAs play roles in tumorigenesis. MiR-26a plays different roles in different types of cancer, and participates in tumor growth, invasion, metastasis, angiogenesis, metabolism, diagnosis and prognosis. This review summarizes the progress of miR-26a study in cancer.

Isothiocyanates (ITCs) are naturally occurring small molecules that are generated by the enzymic hydrolysis of glucosinolate in cruciferous vegetables. Numerous studies showed that ITCs inhibit the growth of tumors by the mechanisms including inducing cell cycle arrest, promoting apoptosis and producing reactive oxygen species in vitro and in vivo. Recent studies showed that ITCs also inhibit metastasis of cancer cells, induce endoplasmic reticulum stress and autophagy. This review summarizes the antitumor mechanisms of ITCs.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic. On one hand, autophagy induced by EGFR-TKI acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR-TKI. On the other hand, a high level of autophagy after treatment of EGFR-TKI can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR-TKI with autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficiency of EGFR-TKI in the treatment of cancer patients. Here we summarized the signaling pathways involved in EGFR-TKI induced autophagy, and reviewed the roles of autophagy in the treatment and chemoresistance of EGFR-TKI treatment in lung cancer.

Background and objective Thymosin beta 10 (Tβ10) is one of β-thymosin family members, has a highly conserved polar 5 kDa peptides. This peptide is now regarded to be a small actin-binding protein and thereby induce depolymerization of the intracellular F-actin networks. Alteration of Tβ10 expression may alter the balance of cell growth, cell death, cell attachment and cell migration. Tβ10 also affects cell metastasis as well as proliferation, apoptosis and vascularization of cancer cells. But function of Tβ10 appear to be rather different between cancer cells, and the molecular mechanisms of β-thymosins to regulate cell apoptosis and proliferation in NSCLC (non-small cell lung cancer) cell lines are unclear. In this study, we used lung adenocarcinoma cell line A549, added Tβ10 or down-regulated the expression of Tβ10. We observed the change of apoptosis, proliferation and cell cyclin ability in A549 and the mechanisms underline them were also identified. Methods After A549 was treated with 100 ng/mL recombinant human Tβ10 or siTβ10, apoptosis rate of A549 and cell cycle distribution were detected by flow cytometry (FCM). CCK-8 assay was employed to determine the proliferation of A549. The mRNA level of P53, Caspase-3, Cyclin A and Cyclin E were determined by real-time PCR. The protein level of P53, Caspase-3, Cyclin A and Cyclin E were detected by Western blot. Results Add Tβ10 can inhibit the apoptosis and prompt the proliferation of A549. It can also increase the cell rates of S-phrase and G2/M-phrase, decrease the expression of P53 and Caspase-3, but increase the expression of Cyclin A and Cyclin E. Interferance of Tβ10 can prompt the apoptosis and inhibit the proliferation of A549. It can also increase the cell rates of G0/G1-phrase, increase the expression of P53 and Caspase-3, but decrease the expression of Cyclin A and Cyclin E. Conclusion In lung cancer cell line, Tβ10 can inhibit the apoptosis by increase P53, drive cells into the S and G2/M-phase, prompt cell proliferation by increase the expression of Cyclin A and Cyclin E. Tβ10 may become a potential biomarker and therapy target for non-small cell lung cancer.

Chemotherapy is one of the primary treatment for malignant tumors. Tumor multidrug resistance (MDR) is a major cause of clinical failure of chemotherapy; however the mechanisms of chemo-resistance have not been fully elucidated. Recently, microRNA is one of the new hotspots in life science. MicroRNA regulates the expression of genes and plays roles a series of life events by post-transcriptional regulations, including cell proliferation, apoptosis, fat metabolism, nervous development, hormone secretion, tumor vessels generation, stem cell differentiation, tumor cell invasion and metastasis, and other physiological and pathological processes. Recent studies show that microRNA regulates the expression of multiple genes with high efficiency and specificity. The abnormal regulation of target genes by microRNA is responsible for tumor chemo-resistance, this may be an important component of the complexity of the regulation of chemo-resistance. Therefore, the study of microRNA and tumor drug resistance has profound practical significance. In this review, recent studies of tumor drug resistance, regulation of tumor drug resistance by microRNA, and microRNA as a potential target for tumor drug resistance therapy are reviewed.

Background and objective Our previous study found that thymosin β10 overexpressed in lung cancer and positively correlated with differentiation, lymph node metastasis and stage of lung cancer. In this reasearch we aim to study the effects and mechanism of exogenous human recombinant Tβ10 on the expression of VEGF-C on non-small cell lung cancer. Methods After SPC, A549 and LK2 cells were treated with 100 ng/mL recombinant human Tβ10, the mRNA level of VEGF-C were detected by RT-PCR. The mean while the protein expression of VEGF-C, P-AKT and AKT were determined by Western blot assay. Results Exogenous recombinant human Tβ10 were significantly promote the expression levels of VEGF-C mRNA and protein while promoting the phosphorylation of AKT. Exogenous Tβ10 can promote the expression of VEGF-C mRNA and protein in lung cancer cell lines A549 and LK2 (P

Background and objective To explore cell lines' difference of drug-resistance to gefitinib and the underlying mechanism. Methods Human lung cancer cell lines of PC9, PC9/AB2, PC9/AB11, PC9/BB4 were treated in vitro , exons 18-21 of EGFR gene were sequenced and EGFR gene mRNA levels were measured. Results Four cell lines' drug resistance difference of gefitinib were validated. All the four cell lines had the 15 bp deletion at exon 19, and AB11 had A to G point-mutation at exon 20. PC9 EGFR gene in the sensitive cell line was expressed much higher than that in 3 resistance cell lines by real-time PCR. Conclusion There is significant difference of drug resistance to gefitinib existed among the lung cancer cell lines PC9, PC9/AB2, PC9/AB11 and PC9/BB4. The mutations changes of expressive level of EGFR gene might be correlated with the acquired drug-resistance to gefitinib in lung cancer cell lines.