MIB2 promotes the progression of non-small cell lung cancer by regulating cell cycle control pathways.

BACKGROUND: Although numerous measures have been used to improve the outcome of lung cancer patients, lung cancer, as the second most common diagnosed cancer, is still the main cause of cancer death. It becomes increasingly urgent for us to deeply deplore the molecular mechanism of lung cancer and to discover the potential therapeutic targets. In our study, we are dedicated to discovering the role of MIB2 in lung cancer development. METHODS: The public databases were used to compare the expression level of MIB2 in cancer and non-cancer tissue. We analyzed the expression of MIB2 in lung cancer samples by performing Rt-PCR and western blot. We carried out CCK8 and clone assays to study the influence of MIB2 in lung cancer proliferation. The transwell assays and wound healing assays were implemented to study the function of MIB2 in metastasis and invasion. Proteins of cell cycle control pathways are detected to verify the potential mechanism of MIB2 in lung cancer progression. RESULTS: MIB2 is up regulated in lung cancer tissue compared to adjacent normal lung tissue according to both public databases and our clinical lung cancer samples. Knockdown of MIB2 inhibits proliferation, metastasis, and invasion of lung cancer cell lines. Cyclins and cyclin dependent kinases (CDK) including CDK2, CDK4, and cyclinB1 were down regulated in MIB2 knockdown cells. CONCLUSION: Our results prove that MIB2 acts as a driver in NSCLC tumorigenesis by regulating cell cycle control pathways.

The effect of lactose and its isomerization product lactulose on functional and structural properties of glycated casein.

Lactulose is an isomer of lactose, formed under thermal processing of milk. Alkaline conditions favor the isomerization of lactose. As reducing sugar, lactose and lactulose could participate in the Maillard reaction and cause protein glycation in milk products. In this study, the influence of lactose and lactulose on the functional and structural properties of glycated casein was investigated. The results demonstrated that compared with lactose, lactulose led to severer changes in molecular weight, more disordered spatial structure and decrease of tryptophan fluorescence intensity of casein. Besides, the glycation degree and advanced glycation end products (AGEs) results suggested that lactulose exhibited stronger glycation ability than lactose due to the higher proportion of open chain in solution. Furthermore, higher glycation degree induced by lactulose resulted in lower solubility, surface hydrophobicity, digestibility and emulsifying capacity of casein-glycoconjugates compared with lactose. The results of this study are essential for tracking the effects of harmful Maillard reaction products on the quality of milk and dairy products.

The effect of B-type procyanidin on free radical and metal ion induced ß-lactoglobulin glyco-oxidation via mass spectrometry and interaction analysis.

Procyanidin is a group of dietary flavonoids abundant in berry fruits. In this study, the effects and underlying mechanisms of B type procyanidin (PC) on free radical and metal ion (H2O2, AAPH and Fe3+) induced milk protein ß-lactoglobulin (BLG) glyco-oxidation were investigated. The results indicated that PC protected BLG structure changes from cross-link and aggregation induced by free radicals and metal ion. Additionally, it effectively inhibited BLG oxidation by reducing approximately 21%-30% carbonyls and 15%-61% schiff base crosslink formation. Also, PC suppressed BLG glycation by inhibiting 48-70% advanced glycation end-products (AGEs) and reduced the accumulation of intermediate product methylglyoxal (MGO). The corresponding mechanisms were elucidated that PC exhibited great free radical scavenging and metal chelating properties; PC had non-covalent bind with the amino acid residues (preferably lysine and arginine) of BLG and blocked them from glycation; PC interrupted BLG glycation by forming procyanidin-MGO conjugates. Therefore, B type procyanidin was an effective glyco-oxidation inhibitor in milk products.

Landscapes of synchronous multiple primary cancers detected by next-generation sequencing.

An increase in the detection rate of multiple primary cancers has been accompanied with declining cancer death rates over the past few decades. However, synchronous multiple primary tumors have gradually increased, and the molecular mechanisms involved in the synchronous occurrence of multiple primary cancers of different origins are unclear. To investigate these mechanisms, we sequenced cancer tissues by FoundationOne CDx. Data were annotated with annovar, and we then performed pathway enrichment analysis. A total of 109 genes that were mutated in all samples were clustered into different diseases, biological processes, and molecular functions. GO and KEGG analyses indicated that the P53 and PKB signaling pathways may be relevant to the occurrence of synchronous multiple primary cancers. In summary, patients with a concordance of mutations in pathogenetic genes may have a higher risk of developing a second cancer. Our research may provide a basis for the development of individualized treatments for synchronous multiple primary cancers.

RPS9 promotes the progression of NSCLC via activation Stat3 and Erk signaling pathways.

Background: Non-small cell lung cancer (NSCLC) accounts for the largest pathological type of lung cancers, and it is characterized by high incidence and poor prognosis. However, the molecular mechanisms involved in development and progression of NSCLC are not well elucidated. In this study, we aimed to explore the role and regulatory mechanism of RPS9 in NSCLC. Materials and methods: The RPS9 expression in NSCLC tissues and cell lines was assessed by qRT-PCR and western blot. Knockdown of RPS9 induced by RNA interference (RNAi) method in PC9, A549 and H1299 cells. Overexpression of RPS9 induced by transient transfection in H292 cells. Cell proliferation, colony formation, metastasis and apoptosis abilities were determined by CCK-8 assay, colony formation assay, transwell assay and flow cytometry, respectively. The host signaling pathways affected by RPS9 were screened by antibody library and proved by western blot. Results: RPS9 was significantly upregulated in NSCLC tissues and cell lines. Overexpression of RPS9 predicted poor prognosis of NSCLC patients. Knockdown of RPS9 obviously repressed cell proliferation, metastasis, and induced apoptosis. Mechanistically, suppression of RPS9 inhibited the expression level of phosphorylation of Stat3 and Erk. Conclusion: Our study clarified that knockdown of RPS9 inhibits the progression of NSCLC via inactivation Stat3 and Erk signaling pathways.