Construction and Analysis of a Mitochondrial Metabolism-Related Prognostic Model for Breast Cancer to Evaluate Survival and Immunotherapy.

As one of the most prevalent malignancies among women, breast cancer (BC) is tightly linked to metabolic dysfunction. However, the correlation between mitochondrial metabolism-related genes (MMRGs) and BC remains unclear. The training and validation datasets for BC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. MMRG-related data were obtained from the Molecular Signatures Database. A risk score prognostic model incorporating MMRGs was established based on univariate, LASSO, and multivariate Cox regression analyses. Independent factors affecting BC prognosis were identified through regression analysis and presented in a nomogram. Single-sample gene set enrichment analysis was employed to assess the immune levels of high-risk (HR) and low-risk (LR) groups. The sensitivity of BC patients in the two groups to common anti-tumor drugs was evaluated by utilizing the Genomics of Drug Sensitivity in Cancer database. 12 MMRGs significantly associated with survival were selected from 1234 MMRGs. A 12-gene risk score prognostic model was built. In the multivariate regression analysis incorporating classical clinical factors, the MMRG-related risk score remained an independent prognostic factor. As revealed by tumor immune microenvironment analysis, the LR group with higher survival rates had elevated immune levels. The drug sensitivity results unmasked that the LR group demonstrated higher sensitivity to Irinotecan, Nilotinib, and Oxaliplatin, while the HR group demonstrated higher sensitivity to Lapatinib. The development of MMRG characteristics provides a comprehensive understanding of mitochondrial metabolism in BC, aiding in the prediction of prognosis and tumor microenvironment, and offering promising therapeutic choices for BC patients with different MMRG risk scores.

miR­204­5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER­2.

Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR­204­5p in gastric cancer. The mRNA expression levels of miR­204­5p in gastric cancer were determined by reverse transcription­quantitative PCR. Cell proliferation was determined using Cell Counting Kit­8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR­204­5p in the 3' untranslated region of human epidermal growth factor receptor 2 (HER­2) was predicted using a bioinformatics algorithm and confirmed using a dual­luciferase reporter assay. miR­204­5p levels were downregulated in gastric cancer cells. Overexpression of miR­204­5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR­204­5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR­204­5p, along with increased expression levels of Bax and decreased expression levels of Bcl­2. HER­2 was a direct target of miR­204­5p, and inhibition of HER­2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR­204­5p expression. These results suggested that miR­204­5p could exert its anti­tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER­2, which may be a potential therapeutic target for gastric cancer.