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Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer-associated mortality. MicroRNA (miR)-576-5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR-576-5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR-576-5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR-576-5p and Wnt5a. Reverse transcription-quantitative PCR and western blotting were used to analyze the expression levels of miR-576-5p, E-cadherin, N-cadherin, vimentin, Snail1, Wnt5a, β-catenin, c-myc, cyclin D1 and p/t-c-Jun. Using bioinformatics analysis, high expression of miR-576-5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR-576-5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial-to-mesenchymal transition (EMT). In addition, miR-576-5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/β-catenin signaling. The results from rescue experiments further demonstrated that the effect of miR-576-5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV-939, which is an inhibitor of the Wnt/β-catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR-576-5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a-mediated Wnt/β-catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.

Matrine, an alkaloid component derived from the Sophora root, can inhibit cancer cell proliferation and induce autophagy via p53 associated pathways. However, numerous tumor cells lack functional p53 and little is known about the effect of matrine on the p53‑deficient/mutant cancer cells. The present study aimed to assess anticancer effects of matrine in p53‑deficient human Hep3B hepatoma cells. The present results demonstrated that matrine caused Hep3B cell apoptosis by suppressing gene expression of minute double‑mutant (MDM)2. Notably, it was revealed that matrine inhibited MDM2 at the transcriptional level in a time‑ and dose‑dependent manner. This MDM2 inhibition resulted in induction of the p53 family member, p73; however, the functions of p73 were not induced since matrine‑induced p73 failed to activate its target genes, p21 and p53 upregulated modulator of apoptosis. The matrine‑induced downregulation of MDM2 led to an inhibition of inhibitor of apoptosis protein 3, which might serve a critical role in matrine‑induced apoptosis in MDM2‑overexpressing Hep3B cells. Finally, combination therapy of matrine with 100 µM epotoside successfully killed more Hep3B cells, suggesting that matrine can sensitize p53‑deficient Hep3B cells to epotoside‑induced apoptosis.

Aromatase inhibitors (AIs) are widely used in the treatment of hormone‑dependent breast cancer and as a result, aromatase inhibitor‑associated bone loss (AIBL) has become a major concern amongst patients receiving AI treatment. Modified Shu‑Gan‑Liang‑Xue decoction (mSGLXD), a clinical prescription, has been used for ameliorating AIBL in patients with breast cancer for decades and has achieved good clinical efficacy. However, the mechanism underlying how mSGLXD influences bone homeostasis and alleviates AIBL has remained elusive. In the present study, mSGLXD was supplemented with Rhizoma Drynariae containing phytoestrogens, and the safety of mSGLXD was evaluated. mSGLXD did not possess estrogenic activity and significantly inhibited the proliferation of estrogen receptor‑positive breast cancer cell line MCF‑7, which suggested that mSGLXD was safe for postmenopausal patients with breast cancer. Subsequently, the effects of mSGLXD alone or in combination with anastrozole on osteoblastic MC3T3‑E1 cell proliferation and differentiation were investigated. Cell counting kit‑8, reverse transcription‑polymerase chain reaction and biochemical methods, such as ELISA and alizarin red S staining, were used in the present study. It was revealed that mSGLXD not only stimulated MC3T3‑E1 cell proliferation, but also upregulated alkaline phosphatase and osteocalcin gene and protein expression levels. High concentrations of anastrozole (10 or 100 µmol/l) markedly inhibited MC3T3‑E1 cell proliferation, but this inhibitory effect was attenuated by mSGLXD. Furthermore, mSGLXD increased MC3T3‑E1 cell mineralization following β‑glycerophosphate and ascorbic acid induction. Therefore, the results of the present study suggested that mSGLXD may be a promising adjuvant therapy, with high safety and efficacy, for the prevention and treatment of AIBL in patients with breast cancer who receive AI treatment.

It has been reported that hsa‑microRNA (miRNA/miR)‑372 functions as a tumor suppressor or oncogene in various digestive system tumors, however, its roles in gallbladder cancer (GBC) are yet to be established. The present study aimed to determine the expression and clinical relevance of hsa‑miR‑372 in GBC. The expression of hsa‑miR‑372 in 80 pairs of human GBC tissues and adjacent normal gallbladder tissues was measured by reverse transcription‑quantitative polymerase chain reaction. Subsequently, the associations between hsa‑miR‑372 expression levels and the clinicopathological characteristics of patients with GBC were determined using χ2 test. Furthermore, Kaplan‑Meier method and Cox regression analysis were performed to evaluate the association between hsa‑miR‑372 expression and the prognosis of patients with GBC. Furthermore, a dual‑luciferase reporter assay and western blot analysis were performed to predict and verify the target gene of hsa‑miR‑372. The results demonstrated that markedly lower hsa‑miR‑372 expression was observed in GBC tissues, which was associated with poor prognosis in patients with GBC. Downregulated expression of hsa‑miR‑372 was negatively associated with tumor histological grade, tumor‑node‑metastasis stage, lymph node metastasis and distant metastasis, however, no association was observed between reduced hsa‑miR‑372 expression and patient gender, age, tumor size and gallbladder stones. Multivariate Cox regression analysis revealed that hsa‑miR‑372 expression, histological grade and lymph node metastasis were independent prognostic factors for overall survival in patients with GBC. Chloride intracellular channel 1 (CLIC1) was previously reported to be an effective biomarker for predicting the prognosis of GBC. Notably, the results of the present study indicated that CLIC1 may be a direct target gene of hsa‑miR‑372. In conclusion, the current study provides the first statistically convincing evidence that downregulation of hsa‑miR‑372 may occur in GBC tissues, which may be associated with aggressive and progressive tumor behavior by affecting CLIC1 expression.

Helicobacter pylori has been suggested to be the major cause of gastric malignancy. However, the pathogenesis and molecular mechanisms of gastric tumorigenesis induced by H. pylori infection are yet to be elucidated. In the present study, the expression levels of vascular endothelial growth factor (VEGF), which has been suggested to promote angiogenesis in gastric cancer, were found to be elevated in H. pylori-infected MKN45 cells. Furthermore, it was demonstrated that the expression of VEGF was modulated by the p38 mitogen-activated protein kinases (MAPK) pathway via regulation of the cyclooxygenase (COX)-2 pathway. It was also found that prostaglandin E2 (PGE2) and its receptor EP2/EP4 may mediate the upregulation of VEGF in gastric cells exposed to H. pylori. In combination, these results suggest that VEGF expression is regulated by the p38 MAPK COX‑2-PGE2-EP2/EP4 pathway in gastric cancer cells induced by H. pylori. This provides a theoretical basis for the investigation of the pathogenesis of H. pylori‑induced gastric cancer.