LINC00857 regulated by ZNF460 enhances the expression of CLDN12 by sponging miR-150-5p and recruiting SRSF1 for alternative splicing to promote epithelial-mesenchymal transformation of pancreatic adenocarcinoma cells.

Recent research unveiled that LINC00857 plays a regulatory role in multiple human cancers, such as lung adenocarcinoma and gastric cancer. Nevertheless, the function of LINC00857 in pancreatic adenocarcinoma (PAAD) remains unclear. This study concentrates on LINC00857 to discuss the relevant molecular mechanism of this gene in PAAD. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were implemented for measuring the expressions of RNAs and proteins. Wound healing and Transwell assays were used to assess cell migration and invasion, and fluorescent in situ hybridization (FISH) to locate LINC00857 in PAAD cells. Additionally, mechanism assays were conducted to validate the interaction between genes. Results indicated that LINC00857 was upregulated in PAAD cells and the knockdown of LINC00857 impeded PAAD cell migration, invasion and epithelial-mesenchymal transition (EMT). Further, it was found that LNC00857 regulates CLDN12 expression by targeting miR-150-5p. Moreover, LINC00857 was confirmed to recruit serine/arginine-rich splicing factor 1 (SRSF1) to promote the alternative splicing (AS) targeting CLDN12, affecting the phenotypes of PAAD cells. In addition, the transcription factor ZNF460 was proven to positively regulate LINC00857 expression. To sum up, LINC00857 regulated by ZNF460 upregulates CLDN12 expression by sponging miR-150-5p and recruiting SRSF1 to facilitate the progression of PAAD cells.[Figure: see text].

Integrated genomic and transcriptomic analysis revealed mutation patterns of de-differentiated liposarcoma and leiomyosarcoma.

BACKGROUND: Treating patients with advanced sarcomas is challenging due to great histologic diversity among its subtypes. Leiomyosarcoma (LMS) and de-differentiated liposarcoma (DDLPS) are two common and aggressive subtypes of soft tissue sarcoma (STS). They differ significantly in histology and clinical behaviors. However, the molecular driving force behind the difference is unclear. METHODS: We collected 20 LMS and 12 DDLPS samples and performed whole exome sequencing (WES) to obtain their somatic mutation profiles. We also performed RNA-Seq to analyze the transcriptomes of 8 each of the LMS and DDLPS samples and obtained information about differential gene expression, pathway enrichment, immune cell infiltration in tumor microenvironment, and chromosomal rearrangement including gene fusions. Selected gene fusion events from the RNA-seq prediction were checked by RT-PCR in tandem with Sanger sequencing. RESULTS: We detected loss of function mutation and deletion of tumor suppressors mostly in LMS, and oncogene amplification mostly in DDLPS. A focal amplification affecting chromosome 12q13-15 region which encodes MDM2, CDK4 and HMGA2 is notable in DDLPS. Mutations in TP53, ATRX, PTEN, and RB1 are identified in LMS but not DDLPS, while mutation of HERC2 is only identified in DDLPS but not LMS. RNA-seq revealed overexpression of MDM2, CDK4 and HMGA2 in DDLPS and down-regulation of TP53 and RB1 in LMS. It also detected more fusion events in DDLPS than LMS (4.5 vs. 1, p = 0.0195), and the ones involving chromosome 12 in DDLPS stand out. RT-PCR and Sanger sequencing verified the majority of the fusion events in DDLPS but only one event in LMS selected to be tested. The tumor microenvironmental signatures are highly correlated with histologic types. DDLPS has more endothelial cells and fibroblasts content than LMS. CONCLUSIONS: Our analysis revealed different recurrent genetic variations in LMS and DDLPS including simultaneous upregulation of gene expression and gene copy number amplification of MDM2 and CDK4. Up-regulation of tumor related genes is favored in DDLPS, while loss of suppressor function is favored in LMS. DDLPS harbors more frequent fusion events which can generate neoepitopes and potentially targeted by personalized immune treatment.

Management of retroperitoneal sarcoma involving the iliac artery: Single-center surgical experience.

BACKGROUND: Management of retroperitoneal sarcoma (RPS) involving the iliac artery is challenging and requires the concerted efforts of multidisciplinary team (MDT) members during surgical treatment. AIM: To summarize the clinicopathologic features of RPS involving the iliac artery and our retroperitoneal soft tissue tumor MDT surgical experience. METHODS: In this retrospective study, 15 patients with RPS involving the iliac artery who underwent surgery at our retroperitoneal soft tissue tumor center from July 2004 to June 2020 were analyzed. Statistical analyses were performed by Student's t-test with SPSS 16.0. RESULTS: Complete tumor resection (R0/R1) and iliac artery reconstruction were achieved in all 15 patients. All the operations were successful, with no serious complications or perioperative death. Resection with bilateral iliac artery reconstruction required a higher intraoperative blood transfusion volume than resection with unilateral iliac artery reconstruction. Recurrent cases were more likely to bleed and required a higher blood transfusion volume than primary cases. As of January 2021, 11 patients were alive, and 4 had died. Local recurrence occurred in two patients, one of whom developed liver metastasis. CONCLUSION: Resection of RPS involving iliac vessels is feasible and effective when performed by MDT members. Iliac artery oncovascular resection and reconstruction are key to a successful operation. Adequate blood preparation is important for successful completion of surgery.

miR-195 Serves as a Tumor Suppressor in the Progression of Liposarcoma by Targeting OSBP.

BACKGROUND: Liposarcoma was considered as a soft tissue kind of sarcoma with one-fifth in the sarcoma cases of adults. The aim of this study was to explore the role and the potential mechanisms of miR-195 in liposarcoma. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of microRNA-195 (miR-195) and oxysterol-binding protein (OSBP) in liposarcoma. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell migration was measured by wound healing and transwell assays. Cell cycle phases and apoptosis were examined using flow cytometry analysis. Caspase-3 activity was detected by commercial kit. Binding sites between miR-195 and OSBP were predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze OSBP level. Xenograft tumor assays were performed to observe the effect of miR-195 overexpression on tumor growth in vivo. RESULTS: miR-195 expression was decreased, whereas OSBP was increased in liposarcoma tissues and cells. Besides, miR-195 upregulation suppressed the proliferative and migrative abilities and induced inhibition on cell growth and promotion on apoptosis in SW872 and 93T449 cells. Mechanically, miR-195 functioned as a suppressor by regulating OSBP expression. Furthermore, OSBP overexpression inverted the effects of miR-195 on cell growth, migration and apoptosis in SW872 and 93T449 cells. miR-195 overexpression also suppressed tumor growth in vivo. CONCLUSION: miR-195 suppressed cell growth, migration and elevated cell apoptosis via OSBP in liposarcoma.

Retracted Article: miR-199a-3p knockdown inhibits dedifferentiated liposarcoma (DDLPS) cell viability and enhances apoptosis through targeting casein kinase-1 alpha (CK1α).

Dedifferentiated liposarcoma (DDLPS) is an aggressive tumor with high mortality. More insight into the biology of DDLPS tumorigenesis is needed to devise novel therapeutic approaches. Previous data showed that miRNA-199a-3p (miR-199a-3p) was strongly upregulated in DDLPS tissues. However, the biological role of miR-199a-3p in DDLPS remains unknown. In this study, we detected miR-199a-3p expression using RT-qPCR and observed that miR-199a-3p was more highly expressed in DDLPS tissues and cell lines (SW872 and LPS141). Functionally, MTT assay, flow cytometry and western blot results demonstrated that knockdown of miR-199a-3p inhibited DDLPS cell viability, enhanced apoptosis rate, and decreased expression of apoptosis-related genes Bax and cleaved caspase 3, as well as increased Bcl-2 expression in vitro. Moreover, xenograft tumors were generated and miR-199a-3p knockdown could suppress DDLPS xenograft tumor growth accompanying decreased proliferating cell nuclear antigen (PCNA) level and increased cleaved caspase 3 level in vivo. Mechanically, luciferase reporter assay and RNA immunoprecipitation (RIP) identified that CK1α was targeted and downregulated by miR-199a-3p. Expression of CK1α was lower in DDLPS tissues. Besides, there was a negative linear correlation between expressions of miR-199a-3p and CK1α in DDLPS tissues. Rescue experiments indicated that CK1α silencing could abolish the effect of miR-199a-3p knockdown on cell viability and apoptosis in DDLPS cells in vitro. In conclusion, knockdown of miR-199a-3p inhibits DDLPS cell viability and enhances apoptosis through targeting CK1α in vitro and in vivo. Our results suggest miR-199a-3p/CK1α axis may be a novel pathogen of DDLPS.

Correction: miR-199a-3p knockdown inhibits dedifferentiated liposarcoma (DDLPS) cell viability and enhances apoptosis through targeting casein kinase-1 alpha (CK1α).

[This corrects the article DOI: 10.1039/C9RA01491H.].

Arsenic oxide targets stem cell marker CD133/prominin-1 in gallbladder carcinoma.

CD133+ tumor cells are responsible for the initiation, propagation and recurrence of tumors, which raises the question of how to effectively target CD133+ tumor cells. Arsenic trioxide (As2O3) has considerable efficacy in treating solid tumors with induction of apoptosis. Here, we found that purified CD133+ gallbladder carcinoma cells are highly resistant to conventional chemotherapy. However, As2O3 effectively induces CD133+ gallbladder carcinoma cells apoptosis. Treatment with As2O3 reduces CD133 expression at transcriptional levels. Furthermore, the ectopic expression of CD133 attenuated the apoptotic effect of As2O3 on cells through activation of AKT signaling pathways. Collectively, As2O3 effectively targets CD133 in gallbladder carcinoma, providing a new mechanism of As2O3-induced cell apoptosis and a better understanding of drug resistance in gallbladder carcinoma.

[Da Vinci robot-assisted gastrectomy with lymph node dissection for gastric cancer: a case series of 9 patients].

OBJECTIVE: To evaluate the technical feasibility, effectiveness, and safety of robot-assisted gastrectomy(RAG) with lymphadenectomy using the Da Vinci system. METHODS: A total of 9 patients in our institute from March 17 to April 24 2010 underwent RAG. Clinicopathologic characteristics and surgical outcomes were summarized. RESULTS: All operations were performed successfully without conversion to either open or laparoscopic approach. There were 5 total gastrectomies,2 distal gastrectomies, 1 proximal gastrectomy and 1 wedge gastrectomy with D(1) or D(2) lymphadenectomy. The total operative time was 150 to 440 minutes. Total blood loss ranged from 10 to 100 ml. The ranges of harvested lymph nodes were 19-24 for D(1) patients and 28-38 for D(2) patients. There was 1 case of postoperative gastric leakage, which were managed conservatively. CONCLUSIONS: RAG with lymphadenectomy can be applied safely and effectively for patients with gastric cancer.