ABSTRACT
Osteosarcoma (OS) is a prevalent primary bone sarcoma. Methyltransferase-like 3 (METTL3) is dysregulated in human malignancies. This study explored the mechanism of METTL3 in OS cell proliferation. Our results demonstrated that METTL3 was highly expressed in OS, and correlated with the tumor size, clinical stage, and distant metastasis of OS patients. Higher METTL3 expression indicated poorer prognosis. METTL3 silencing inhibited the malignant proliferation of OS cells, while METTL3 overexpression led to an opposite trend. METTL3 upregulated histone deacetylase 5 (HDAC5) expression in OS cells by increasing the m6A level. HDAC5 reduced the enrichment of H3K9/K14ac on miR-142 promoter, thus suppressing miR-142-5p expression and upregulating armadillo-repeat-containing 8 (ARMC8) level. HDAC5 overexpression or miR-142-5p silencing attenuated the inhibitory effect of METTL3 silencing on OS cell proliferation. Xenograft tumor experiment in nude mice confirmed that METTL3 silencing repressed OS cell proliferation in vivo via the HDAC5/miR-142-5p/ARMC8 axis. Collectively, METTL3-mediated m6A modification facilitated OS cell proliferation via the HDAC5/miR-142-5p/ARMC8 axis.
ABSTRACT
BACKGROUND: Acral lentiginous melanoma (ALM) is common in China with poor prognosis. However, there are only a few studies of ALM in the Asian population. We aimed to summarize and analyze the clinical characteristics, treatment strategy, treatment effect, and prognostic factors of ALM in a Chinese population. METHODS: We included a total of 249 ALM patients (211 with follow-up data) from a single institution. Demographic, laboratory data, treatment strategy, and prognosis were analyzed. RESULTS: The ratio of male and female was 1.3 ⶠ1.0. The median age was 58 years old. The majority of patients (70.3%) had lesions on the sole. Trauma history and irritation were associated with lesion size increase in some patients. The prognosis of patients in stage II-III undergoing standard operation was significantly better compared with those without surgical treatment. Patients who did not receive postoperative adjuvant treatment had shorter time to distant metastasis. In multivariable analysis, distant metastasis, duration of disease, LDH level, and Ki67 index were independently associated with survival. CONCLUSIONS: Prognosis for ALM patients was poor in our study. Distant metastasis, duration of disease, LDH level, and Ki67 index were independently associated with prognosis.
Subject(s)
Melanoma , Skin Neoplasms , China/epidemiology , Female , Humans , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
Objective: The purpose of this study was to explore the feasibility and clinical applicability of a modified type V resection method for malignant bone tumors of the proximal humerus. Methods: The relevant anatomic MRI data from 30 normal adult shoulder joints were measured to analyze the feasibility of the modified type V resection method for malignant bone tumors of the proximal humerus. Sixteen patients with malignant bone tumors of the proximal humerus were treated with modified radical resection between March 2012 and April 2017. Recurrence of tumor was evaluated after surgery, and shoulder function was assessed according to the Enneking skeletal muscle tumor function scoring system. Results: Radiographic results showed that the modified type V resection method was feasible, and within the allowable range of the maximum longitudinal diameter (<29.8 mm) and depth (<4 mm). Surgery was successfully completed in all 16 cases, and pathological examination suggested that the purposes for radical resection had been achieved. All patients were followed up over 3-49 months (mean, 15.6 months). One patient had local recurrence at 12 months after surgery, and we performed upper limb amputation. The remaining 15 patients had good prosthesis survival. At the final follow-up, shoulder joint function had recovered compared with preoperative levels, with a mean Enneking score of 25.8 points (range, 24-27 points). Conclusion: Modified type V resection may be feasible for treating tumors of the proximal humerus, maintaining good early shoulder function.
