SH3BP1 Regulates Melanoma Progression Through Race1/Wace2 Signaling Pathway.

Background: SH3-domain binding protein-1 (SH3BP1), which specifically inactivates Rac1 and its target protein Wave2, has been shown to be an important regulator of cancer metastasis. However, the effects of SH3BP1 in melanoma progression remain unclear. The current study aimed to explore the function of SH3BP1 in melanoma and its possible molecular mechanism. Methods: TCGA database was used to analyze the expression of SH3BP1 in melanoma. Then, reverse transcription-quantitative polymerase chain reaction was performed to detect the expression of SH3BP1 in melanoma tissues and cells. Next, genes related to SH3BP1 were analyzed by LinkedOmics database, and protein interactions were analyzed by STRING database. These genes were further subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In addition, the signaling pathway of SH3BP1 action was screened by bioinformatics analysis. Finally, the function of SH3BP1 and its mediated signaling pathway in melanoma progression were investigated in vitro and in vivo. Results: SH3BP1 was significantly upregulated in melanoma tissues and cells. The pathways regulated by SH3BP1 are closely related to the occurrence and development of tumors. And we found that overexpression of SH3BP1 promoted the proliferation, migration, and invasion of melanoma cells by increasing Rac1 activity and Wave2 protein levels in vitro. Similarly, overexpression of SH3BP1 facilitated melanoma progression by upregulating Wave2 protein expression in vivo. Conclusion: In summary, this study revealed for the first time that SH3BP1 promoted melanoma progression through Rac1/Wave2 signaling pathway, providing a new therapeutic target for melanoma.

Evaluation of the prognostic role of platelet-lymphocyte ratio in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

OBJECTIVE: Whether platelet-lymphocyte ratio (PLR) is a prognostic factor for cancer patients treated with immunotherapy is under debate. In this study, we aimed to evaluate the relationship between PLR and survival of cancer patients treated with immune checkpoint inhibitors (ICIs). METHODS: A systematical search was performed in databases including PubMed, Embase, and the Cochrane library to retrieve potential eligible clinical studies assessing the prognosis of cancer patients with high versus low PLR after immunotherapy, from the establishment of the database to June 2019. Quality evaluation of included studies was performed, and meta-analyses with regards to overall survival (OS) and progression-free survival (PFS) were conducted using RevMan 5.3 and STATA 11. RESULTS: A total of 12 eligible studies with 1340 cancer patients were included. Combined results showed that elevated PLR was a negative factor affecting the efficacy of ICIs in cancer patients. Patients with high PLR had a significantly shorter OS compared to those with low PLR (hazard ratio (HR) = 2.02, 95% confidence interval (CI): 1.46 to 2.80, P < 0.0001), as well as PFS (HR = 1.74, 95%CI: 1.27 to 2.38, P = 0.0006). Similar results were observed in sensitivity analyses. Subgroup analyses revealed that the prognostic role of PLR on OS and PFS was dependent on cancer type, region, and cutoff value. For NSCLC patients, the disease stage, ICIs agent, and line of treatment may not influence the prognostic role of PLR. CONCLUSION: PLR could be a routinely potential prognostic factor for ICIs. Low PLR may be associated with better survival for cancer patients when treated with immunotherapy.

LncRNA WWOX­AS1 inhibits the proliferation, migration and invasion of osteosarcoma cells.

Recently, numerous long non­coding (lnc)RNAs have been revealed as serving important roles in human gene regulation. Previous studies have suggested that aberrant expression of lncRNAs is associated with cancer progression and metastasis. Previous studies have also demonstrated that decreased expression of WW domain­containing oxidoreductase (WWOX) is associated with poor prognosis in numerous cancer types. However, the effect of WWOX antisense RNA 1 (WWOX­AS1) in the development of cancer remains unknown. The aim of the present study was to investigate the role of WWOX­AS1 in osteosarcoma. The expression levels of WWOX­AS1 in human osteosarcoma cell lines and a normal osteoblastic cell line were investigated using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The results revealed that WWOX­AS1 expression was downregulated in osteosarcoma tissues. Furthermore, the association between WWOX­AS1 and the prognosis of patients with osteosarcoma was investigated using Kaplan­Meier and log­rank tests. The results suggested that patients exhibiting high WWOX­AS1 expression demonstrated a greater overall survival compared with patients exhibiting low WWOX­AS1 expression. In addition, overexpression and knockdown of WWOX­AS1 was performed using transfection experiments and confirmed by RT­qPCR in MG63 and SAOS2 cells, respectively. The results demonstrated that WWOX­AS1 and WWOX expression were positively correlated. Furthermore, the results of the knockdown and overexpression functional experiments suggested that WWOX­AS1 overexpression inhibited the proliferation, migration and invasion of MG63 cells, and knockdown of WWOX­AS1 enhanced the proliferation, migration and invasion of MG63 cells in SAOS2 cells. In conclusion, the results of the present study suggested that WWOX­AS1 may represent a potential biomarker and therapeutic target for the treatment of osteosarcoma.

A new tumor suppressor lncRNA RP11-190D6.2 inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells.

At present, a large number of long noncoding RNAs (lncRNAs) from the human genome have been discovered. Meanwhile, emerging evidence has indicated that lncRNAs could play a critical role in the regulation of cellular processes such as cancer progression and metastasis. However, the functions of some new lncRNAs in the complex transcriptional process are mostly unknown at present. Existing studies suggest that loss of WW domain-containing oxidoreductase (WWOX) expression is linked with poor prognosis in numerous cancers, including epithelial ovarian cancer (EOC). However, the functional role of its antisense transcript RP11-190D6.2 is not clear to date. In this study, WWOX antisense transcript RP11-190D6.2 was analyzed specifically in EOC cells using real-time polymerase chain reaction and gain-/loss-of-function studies. We found that RP11-190D6.2 expression was positively correlated with WWOX expression. The RP11-190D6.2 expression was markedly downregulated in tumor tissues compared with normal tissues, but the RP11-190D6.2 expression was significantly downregu-lated in four EOC cell lines compared with human ovarian surface epithelial cell line. RP11-190D6.2 overexpression resulted in the increase of WWOX expression, whereas its knockdown led to the decrease of WWOX expression. We also found that RP11-190D6.2 was restored by 5-aza-2'-deoxycytidine treatment in EOC. In addition, the RP11-190D6.2 overexpression and knockdown experiments revealed that RP11-190D6.2 overexpression inhibited proliferation, migration, and invasion abilities in HO8910-PM cells, whereas RP11-190D6.2 knockdown in HEY-A8 cells had the opposite effect. The analyses in EOC implicate that RP11-190D6.2 may play a pivotal role in the regulation of tumor metastasis, suggesting that RP11-190D6.2 may serve as a potential biomarker and therapeutic target for EOC.