MicroRNA-215-5p promotes proliferation, invasion, and inhibits apoptosis in liposarcoma cells by targeting MDM2.

BACKGROUND: Liposarcoma (LPS) is one of the most common soft tissue malignancies in adults, and it is characterized by dysregulation of multiple signaling pathways, including MDM2 proto-oncogene (MDM2) amplification. MicroRNA (miRNA) regulates gene expression through incomplete complementary pairing with the 3' untranslated region of mRNAs involved in tumor progression. METHODS: In this study, bioinformatics analysis, RT-qPCR, dual-luciferase reporter gene, MTT, flow cytometry, cell scratches, chamber migration, colony formation, FISH, WB, and CCK8 were used. RESULTS: RT-qPCR showed that the expression of MDM2 was increased when miR-215-5p was overexpressed compared with the control group. The dual-luciferase reporter gene showed that the Renilla ratio firefly fluorescence intensity was decreased in the overexpression group compared with the control group. Cell phenotype experiments revealed that the overexpression group had increased cell proliferation rate, increased apoptosis rate, increased colony formation rate, increased cell healing area ratio, and increased number of cell invasions. FISH revealed increased MDM2 expression in the overexpression group. WB suggested decreased Bax expression, increased PCNA, Bcl-2, and MDM2 expression, and decreased P53 and P21 expression in the overexpression group. CONCLUSIONS: In this study, we suggest that miR-215-5p can target and promote MDM2 expression, promote the proliferation and invasion of LPS cells SW-872, and inhibit apoptosis.Targeting miR-215-5p may be a novel therapeutic strategy for the treatment of LPS.

METTL3 stabilizes HDAC5 mRNA in an m6A-dependent manner to facilitate malignant proliferation of osteosarcoma cells.

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.

Clinical characteristics and prognosis of acral lentiginous melanoma: a single-center series of 211 cases in China.

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 ∶ 1.0. 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.

Feasibility Analysis and Clinical Applicability of a Modified Type V Resection Method for Malignant Bone Tumors of the Proximal Humerus.

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.

Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients.

Circulating tumor cells (CTCs) have emerged as promising tools for noninvasive cancer detection and prognosis. Most conventional approaches for capturing CTCs use an EpCAM-based enrichment strategy, which does not work well in cancers that show low or no expression of EpCAM, such as renal cell carcinoma (RCC). In this study, we developed a new set of cell surface markers including CA9 and CD147 as alternative CTC-capture antigens specifically designed for RCC patients. We showed that the expression of both CA9 and CD147 was prevalent in a RCC patient cohort (n=70) by immunohistochemical analysis, with both molecules in combination covering 97.1% of cases. The NanoVelcro platform combined with CA9-/CD147-capture antibodies demonstrated significantly higher efficiency for capturing both CTC-mimicking renal cancer cells and RCC CTCs in peripheral blood, compared to the conventional EpCAM-based method. Using immunofluorescence cytological validation at the single-cell level, we were able to identify bona fide CTCs in RCC patient blood following the well-accepted criteria in our CTC-capture system. We further demonstrated a significant association of CTC numbers as well as the CTC expression status of Vimentin, a mesenchymal marker, with disease progression, including pathologic features and clinical staging. These results provide new insights into developing novel, effective targets/approaches for capturing CTCs, making CTCs a valuable tool for improved cancer detection, prognosis and treatment in RCC.