MiR-1246 regulates the PI3K/AKT signaling pathway by targeting PIK3AP1 and inhibits thyroid cancer cell proliferation and tumor growth.

One of the most prevalent forms of endocrine malignancies is thyroid cancer. Herein, we explored the mechanisms whereby miR-1246 is involved in thyroid cancer. Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1) was identified as a potential miR-1246 target, with the online Gene Expression Omnibus (GEO) database. The binding between miR-1246 and PIK3AP1 and the dynamic role of these two molecules in downstream PI3K/AKT signaling were evaluated. Analysis of GEO data demonstrated significant miR-1246 downregulation in thyroid cancer, and we confirmed that overexpression of miR-1246 can inhibit migratory, invasive, and proliferative activity in vitro and tumor growth in vivo. Subsequent studies indicated that miR-1246 overexpression decreased the protein level of PIK3AP1 and the phosphorylation of PI3K and AKT, which were reversed by PIK3AP1 overexpression. At the same time, overexpression of PIK3AP1 also reversed the miR-1246 mimics-induced inhibition proliferative, migratory, and invasive activity, while promoting increases in apoptotic death, confirming that miR-1246 function was negatively correlated with that of PIK3AP1. Subsequently, we found that the miR-1246 mimics-induced inhibition of PI3K/AKT phosphorylation was reversed by the PI3K/AKT activator IGF-1. miR-1246 mimics inhibited proliferative, migratory, and invasive activity while promoting increases in apoptotic death, which were reversed by IGF-1. Furthermore, miR-1246 agomir can inhibit tumor growth in vivo. We confirmed that miR-1246 affects the signaling pathway of PI3K/AKT via targeting PIK3AP1 and inhibits the development of thyroid cancer. Thus, miR-1246 is a new therapeutic target for thyroid cancer.

The Effects of Placental Mesenchymal Stem Cells Labeled With Ultrasmall Superparamagnetic Iron Oxides on the Growth of Colorectal Cancer Cells.

OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, with effective intervention and treatment being essential for CRC management. This study investigated the effects of human placental mesenchymal stem cells (PMSCs) labeled with ultrasmall superparamagnetic iron oxides (USPIOs) on the growth of CRC cells and the feasibility of 3.0-T magnetic resonance (MR) imaging as an in vivo tracer. METHODS: Twenty subcutaneous CRC HT-29 xenograft model in immunodeficient mice was established. Mice injected with labeled PMSCs were considered as the experimental group. Thereafter, the growth and MR signal changes of xenograft tumors of every nude mouse were measured. Then, growth curve was plotted, and the MR image quality in different sequences was analyzed. Pathological staining was performed after MR scan. RESULTS: Ultrasmall superparamagnetic iron oxides-labeled PMSCs had no significant influence on biological characteristics ( P > 0.05). The growth of tumors in mice in the experimental group before the injection of PMSCs was similar to that of the control group. Contrarily, the tumor growth rate in the experimental group on day 5 post-PMSCs injection was slightly lower than that of the control group. Moreover, the tumor volume on day 14 was noticeably smaller than in the control group. The tracing ability of T2* mapping sequences for USPIOs-labeled cells was significantly more effective than T2-weighted image and T2 mapping sequences. CONCLUSIONS: Ultrasmall superparamagnetic iron oxides-labeled PMSCs injected into CRC transplanted tumors can be studied for a long period of time. Furthermore, 3.0-T MRI in vivo molecular imaging was demonstrated to be effective for CRC intervention.

Is 18F-FDG PET/CT Beneficial for Newly Diagnosed Breast Cancer Patients With Low Proportion of ER Expression?

OBJECTIVE: It is unclear whether the receptor status of breast malignancy or the proportion of receptors expression is useful in the interpretation of 18F-FDG PET/CT. This study's purpose was to analyze whether 18F-FDG PET/CT was valuable for helping newly diagnosed breast cancer patients find suspected or unsuspected metastasis lesions based on the proportion of receptors expression. MATERIALS AND METHODS: Eighty newly diagnosed breast cancer patients were divided into six groups, containing N0 (no extraaxillary lymph node metastasis), N1 (extraaxillary lymph node metastasis), M0 (no distant metastasis), and M1 (distant metastasis) groups, C0 (no unsuspected metastasis), and C1 (unsuspected metastasis and treatment plan changed) detected by PET/CT. The main data, including the proportion of receptors ER (estrogen receptor), PR (progesterone receptor), and Her-2 (human epidermal growth factor receptor 2) status, were extracted. Simple correlation and logistic regression were preformed to analyze the association between them. RESULTS: Patients in N1 group had lower proportion of ER (%) and PR (%) than that in N0 group (ER: 2 [0-80] vs. 80 [15-95]; PR: 1 [0-10] vs. 20 [0-45], p<0.001). Moreover, the proportions of ER and PR were negatively correlated with N1 (ER: [r= -0.339, p= 0.002], PR: [r= -0.247, p= 0.011]) by simple correlation. Also, patients in C1 group had lower proportion of ER (%) and PR (%) than those in C0 group (ER: 10 [0-85] vs. 80 [15-90], p=0.026; PR: 1 [0-10] vs. 20 [0-70], p=0.041), while the distribution of ER and PR between M1 and M0 group had no significant difference. After the adjustment of traditional factors, the negative correlation between the proportion of ER (OR=0.986, 95% CI of OR [0.972-0.999], p=0.016) and C1 was found by logistic regression, cutoff value was 25% (ER) calculated by ROC (Receiver Operating Characteristic) curve (AUC [Area Under Curve]= 0.647, p=0.024). CONCLUSION: The proportion of ER in newly diagnosed breast cancer was negatively correlated with unsuspected metastasis detected by 18F-FDG PET/CT. 18F-FDG PET/CT might be recommended for newly diagnosed breast cancer patients with single lesions when the ER expression proportion is less than 25% to find unsuspected metastasis lesions and to modify treatment plan contrasted with conventional imaging and clinical examination.