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Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC. [ABSTRACT FROM AUTHOR]

Hypoxic microenvironment commonly occurred in the solid tumors considerably decreases the chemosensitivity of cancer cells. Salidroside (Sal), the main active ingredient of Rhodiola rosea, was shown to be able of regulating the tumor hypoxia micro-environment and enhancing the chemotherapeutic efficacy of drug-resistant cancer. Therefore, in this study, the Sal was co-loaded with Apatinib (Apa) by the PLGA-based nanoparticles (NPs) to improve the chemosensitivity of gastric cancer cells. Additionally, to improve the drug delivery efficacy, the tumor-homing peptide (iVR1 peptides) was further decorated on the surface of NPs. The tumor targeting ability of the peptides-functionalized nanoparticles (iVR1-NPs-Apa/Sal) was evaluated by in vitro and in vivo experiments. As the obtained results revealed that the iVR1-NPs-Apa/Sal displayed excellent tumor affinity than the unmodified ones (NPs-Apa/Sal), which in turn resulted in more efficient of anti-proliferation of gastric cancer cells and anti-tumor effect in vivo. In addition, compared with the cells or tumor-bearing mice only treaded by monotherapy of Apa, the cells or mice received combinational treatment of Apa and Sal showed obvious lower rate of growth, invasion, and migration or tumor growth and progress. Underlying mechanisms were further investigated and it was revealed that the anti-gastric cancer effect of Apa was signally improved by Sal through down-regulation the proliferation factors and increase the pro-apoptotic genes, as well as reprograming the tumor hypoxia micro-environment. In a word, the study showed that the Sal was able of improving the chemosensitivity of gastric cancer to Apa and the iVR1-NPs-Apa/Sal was capable of realizing highly efficient of tumor-targeting drug delivery. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the most common causes of cancer death. Hypoxia is an important property of the tumor microenvironment of GC. Increasing evidence demonstrates that tumor-associated macrophages are related to the metastasis of GC, while the precise mechanism of how hypoxic macrophages affect tumor progression is still not fully understood.Aims: To examine whether the mediators released from hypoxic macrophages contribute to the invasion and proliferation of GC cells.Methods: Cell Counting Kit-8 was utilized to determine the proliferation of SGC7901 and MKN45 cells. The invasion of SGC7901 and MKN45 cells was measured by transwell invasion assay. Expression of VEGF mRNA in THP-1-derived macrophages was determined by RT-PCR, and protein level of VEGF in the culture medium was detected by ELISA.Results: The proliferation and invasion of SGC7901 and MKN45 cells were dramatically increased after treatment with conditioned medium (CM) collected from THP-1-derived macrophages under hypoxia (H-CM), and the phosphorylation of Akt and p38 in SGC7901 and MKN45 cells was also up-regulated by H-CM stimulation. Notably, blockage of PI3K-Akt or p38 MAP kinase abolished the effects of H-CM on the proliferation and invasion of SGC7901 and MKN45 cells. Furthermore, VEGF was increased in macrophages after hypoxia and administration with nintedanib, an inhibitor of VEGFR, significantly decreases the phosphorylation of Akt and p38, as well as the proliferation and invasion of SGC7901 and MKN45 cells in response to H-CM.Conclusions: Our findings suggest that hypoxia-injured macrophages contribute to the proliferation and invasion of GC cells through the release of mediators such as VEGF. [ABSTRACT FROM AUTHOR]