ABSTRACT
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.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Prognosis , Immunotherapy , Genetic Risk Score , Tumor Microenvironment/geneticsABSTRACT
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.