Pterostilbene (trans-3,5-dimethoxy-4′-hudroxystilbene) is an antioxidant primarily found in blueberries. It also inhibits breast cancer regardless of conventional estrogen receptor (ER-α66) status by inducing both caspase-dependent and caspase-independent apoptosis. However, the pterostilbene-induced apoptosis rate in ER-α66-negative breast cancer cells is much higher than that in ER-α66-positive breast cancer cells. ER-α36, a variant of ER-α66, is widely expressed in ER-α66-negative breast cancer, and its high expression mediates the resistance of ER-α66-positive breast cancer patients to tamoxifen therapy. The aim of the present study is to determine the relationship between the antiproliferation activity of pterostilbene and ER-α36 expression in breast cancer cells. Methyl-thiazolyl-tetrazolium (MTT) assay, apoptosis analysis, and an orthotropic xenograft mouse model were used to examine the effects of pterostilbene on breast cancer cells. The expressions of ER-α36 and caspase 3, the activation of ERK and Akt were also studied through RT-PCR, western blot analysis, and immunohistochemical (IHC) staining. ER-α36 knockdown was found to desensitize ER-α66-negative breast cancer cells to pterostilbene treatment both in vitro and in vivo, and high ER-α36 expression promotes pterostilbene-induced apoptosis in breast cancer cells. Western blot analysis data indicate that MAPK/ERK and PI3K/Akt signaling in breast cancer cells with high ER-α36 expression are mediated by ER-α36, and are inhibited by pterostilbene. These results suggest that ER-α36 is a therapeutic target in ER-α36-positive breast cancer, and pterostilbene is an inhibitor that targets ER-α36 in the personalized therapy against ER-α36-positive breast cancer.

Radiotherapy significantly increases survival innumerous cancer patients, although it may have delayed adverse effects, including significant short‑ and long‑term effects on cardiovascular function, leading to significant morbidity and mortality. However, the mechanisms underlying these effects remain unclear. Cardiomyocyte senescence contributes to cardiovascular disease via impaired cardiac function. MicroRNA‑34a (miR‑34a) is a senescence‑associated miR involved in the pathology of cardiovascular diseases, while macrophage migration inhibitory factor (MIF) is a cardioprotective cytokine with an important role in cardiovascular diseases. The present study aimed to determine whether MIF has a cytoprotective effect in cardiomyocytes exposed to radiation through modulating miR‑34a. Human cardiomyocytes (HCMs) were incubated with MIF and then exposed to radiation. Cellular proliferation was measured using a Cell Counting Kit‑8, while cellular senescence was evaluated based on the senescence‑associated β‑galactosidase activity and the gene expression levels of cyclin‑dependent kinase inhibitor 1a (Cdkn1a) and Cdkn2c. Oxidative stress was evaluated by measuring the generation of reactive oxygen species and malondialdehyde, as well as the expression of antioxidant genes. In addition, HCMs were treated with small interfering RNA against sirtuin 1 (SIRT1) to examine the role of this gene in MIF‑associated rejuvenation following radiation‑associated senescence. miR‑34a was significantly increased in HCMs exposed to radiation, while MIF inhibited senescence by suppressing miR‑34a. SIRT1 was identified as a target gene of miR‑34a, mediating the anti‑senescence effect induced by MIF. Furthermore, MIF rejuvenation involved rebalancing the oxidation process disturbed by radiation. These results provided direct evidence that inhibition of miR‑34a by MIF protected against radiation‑induced cardiomyocyte senescence via targeting SIRT1. Inhibition of miR‑34a by MIF may thus be a novel strategy for combating cardiac radiation‑associated damage.

The sirtuins (SIRTs) are a family of nicotinamide-adenine dinucleotide (NAD)+-dependent protein deacetylases. SIRT4 is a mitochondrial NAD+-dependent adenosine diphsophate-ribosyltransferase. Recent studies demonstrated that SIRT4 can regulate glutamine metabolism and thus act as a tumor suppressor. However, the association of SIRT4 with gastric cancer remains unknown. The present study investigated the potential role of SIRT4 in the proliferation of human gastric cancer cells. Gastric cancer cell lines (SGC-7901 and MNK45) overexpressing SIRT4 were established by lentiviral infection. The effect of overexpression of SIRT4 in gastric cancer was evaluated by determining the cell viability, proliferation activity and colony-forming ability of gastric cancer cells in vitro. Furthermore, the cell cycle profiles of SGC-7901 and MNK45 cells overexpressing SIRT4 were evaluated to provide insights into potential underlying molecular mechanisms. Overexpression of SIRT4 significantly inhibited the proliferation and colony-forming ability of the gastric cancer cells in vitro. Furthermore, overexpression of SIRT4 induced G1 cell cycle arrest via suppression of phosphorylated extracellular signal-regulated kinase, cyclin D and cyclin E. In conclusion, the results of the present study indicated that SIRT4 may function as a tumor suppressor in gastric cancer by regulating cell proliferation, therefore SIRT4 may be a potential therapeutic target against this disease.

Colorectal cancer metastasis is believed to be associated with microRNA dysregulation. However, little is known as to how microRNAs regulate colorectal cancer proliferation, invasion and metastasis. In the present study, we compared the microRNA expression profiles between patients of colorectal cancer at diagnosis with and without liver metastasis. MicroRNA-320b was found to be among those up-regulated in the patient group with metastasis. We subsequently found that microRNA-320b, opposite of its homolog, microRNA-320a that differs by only a single nucleotide, functions in promoting colorectal cancer cell proliferation and invasion. Moreover, we found that overexpression of exogenous microRNA-320b can up-regulate the target genes of microRNA-320a including β-catenin, Neuropilin-1 and Rac-1, which are all known to promote tumor proliferation, invasion and metastasis. These results suggest that microRNA-320b may function in competing with microRNA-320a. Thus, our study has proposed one novel mechanism for controlling colorectal cancer proliferation and invasion through homologous competition between microRNAs. This mechanism may be important for colorectal cancer metastasis.