SOX4-activated lncRNA MCM3AP-AS1 aggravates osteoarthritis progression by modulating miR-149-5p/Notch1 signaling.

OBJECTIVE: To clarify the expression and underlying network of long non-coding RNA (lncRNA) MCM3AP-AS1 in osteoarthritis (OA). METHODS: Human articular cartilage samples, OA model rats and IL-1ß-treated C28/I2 cells were used in this study. The expression changes of genes and proteins were assessed by real-time quantitative PCR (qRT-PCR) and western blot. Cell viability, apoptosis, autophagy and extracellular matrix (ECM) degradation were assessed by Cell Counting Kit-8 (CCK-8), immunohistochemistry (IHC), flow cytometry, immunofluorescence and western blot assays, respectively. Molecule interactions were validated by dual luciferase and Chromatin immunoprecipitation (ChIP) assays. H&E staining was used to detect the pathological changes of cartilage. RESULTS: MCM3AP-AS1 was upregulated in OA patients and IL-1ß-induced chondrocytes. Knockdown of MCM3AP-AS1 enhanced autophagy, while alleviated ECM degradation and cartilage injury. Mechanistically, overexpression of SOX4 boosted the transcription of MCM3AP-AS1. Moreover, MCM3AP-AS1 functioned as a molecular sponge or epigenetic regulator of miR-149-5p to facilitate Notch1 expression. Functional rescue experiments showed that either inhibition of miR-149-5p nor ectopic expression of Notch1 dramatically weakened the biological impacts of MCM3AP-AS1 silencing. CONCLUSION: These finding demonstrated that SOX4-activated MCM3AP-AS1 aggravated OA progression by modulating autophagy and ECM degradation via targeting miR-149-5p/Notch1 axis. These data supported that inhibition of MCM3AP-AS1 might be a potential treatment strategy of OA.

Nasopharyngeal carcinoma treated by radical radiotherapy alone: Ten-year experience of a single institution.

PURPOSE: To report on our experience in the treatment of nasopharyngeal carcinoma (NPC) by radical radiotherapy alone in our institution during the last decade. METHODS AND MATERIALS: From January 1990 to May 1999, 905 NPC patients were treated and were studied retrospectively. Radical radiotherapy was given to this cohort by conventional technique in a routine dose of 70-72 Gy to the primary tumor and metastatic lymph nodes. In case of residual primary lesion, a boost dose of 8-24 Gy was delivered by either 192Ir afterloading brachytherapy, fractionated stereotactic radiotherapy, conformal radiotherapy, or small external-beam fields. RESULTS: The 5-year and 10-year local-regional control, overall survival, and disease-free survival rates were 81.7% and 76.7%, 76.1% and 66.5%, 58.4% and 52.1%, respectively. In case of residual primary lesions after a dose of 70-72 Gy of conventional external-beam radiotherapy (EBRT), an additional boost was able to achieve a local control of 80.8%, similar to that obtained with primary lesions that completely disappeared at 70-72 Gy (82.6%, p = 0.892). CONCLUSIONS: The treatment results of radical EBRT followed by a boost dose to the residual primary tumor for nasopharyngeal carcinoma in our institution are promising.

Update report of T4 classification nasopharyngeal carcinoma after intensity-modulated radiotherapy: an analysis of survival and treatment toxicities.

OBJECTIVE: To evaluate the long-term survival outcomes and toxicity of a larger series of patients with non-metastatic T4 classification nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: From March 2004 to June 2011, 335 non-metastatic T4 classification NPC patients treated by IMRT were analyzed retrospectively. Treatment induced toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: With a median follow-up time of 53.6 months (range, 2.8-114.9 months), the 5-year local failure-free survival (LFFS), regional failure free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) were 84.1%, 92.2%, 74.1%, and 63.0%, respectively. At their last follow-up visit, 118 patients (35.2%) had developed treatment failure. Distant metastasis was the major failure pattern after treatment. The most common toxicities were mainly in grade 1 or 2. Concurrent chemotherapy failed to improve survival rates for patients with T4 classification NPC. CONCLUSION: The results of T4 classification NPC treated by IMRT were excellent, and distant metastasis was the most commonly failure pattern. Treatment-related toxicities were well tolerable. The role of concurrent chemotherapy for T4 classification NPC needs to be further investigated in the era of IMRT.