METTL3 upregulates COPS5 expression in osteosarcoma in an m6A-related manner to promote osteosarcoma progression
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Long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB) is a novel lncRNA, which is recently reported to have critical roles in carcinogenesis and progression of several cancers. However, the expression, clinical values, biological roles, and underlying molecular mechanisms of lncRNA-ATB in osteosarcoma are still known. In this study, we measured lncRNA-ATB expression in serum and osteosarcoma tissues of osteosarcoma patients, analyzed its diagnostic and prognostic values. Serum lncRNA-ATB is increased in osteosarcoma patients and could accurately discriminate osteosarcoma patients from healthy controls. LncRNA-ATB is also upregulated in osteosarcoma tissues and cell lines, and positively associated with Enneking stage, metastasis and recurrence. Increased lncRNA-ATB level indicates poor recurrence-free survival and overall survival. Functional experiments demonstrated that overexpression of lncRNA-ATB enhances osteosarcoma cells proliferation, migration, and invasion, and while depletion of lncRNA-ATB inhibits osteosarcoma cells proliferation, migration, and invasion. Mechanistically, we found that lncRNA-ATB inhibits miR-200s, and upregulates miR-200s target genes ZEB1 and ZEB2. Additionally, the roles of lncRNA-ATB on osteosarcoma cells proliferation, migration, and invasion in vitro, and osteosarcoma tumor growth in vivo are dependent on the regulation of miR-200s. Taken together, this study suggests that lncRNA-ATB may be a potential diagnostic and prognostic biomarker and a therapeutic target for osteosarcoma.
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KRT81 is involved in carcinogenesis and progression of many types of human cancers. However, little is known about the role of KRT81 in melanoma. In this study, we identified that KRT81 expression is upregulated in melanoma tissues compared with corresponding adjacent nontumor tissues. Overexpression of KRT81 was also found in human melanoma cell lines. Cell functional studies have shown that KRT81 knockdown could inhibit proliferation, colony formation, migration, invasion, and promote apoptosis of A375 cells. Consistently, in vivo tumorigenesis experiments showed that KRT81 knockdown significantly suppressed the growth of xenograft tumors. Moreover, KRT81 knockdown increased the chemosensitivity of A375 cells to DDP. Mechanical exploration revealed that KRT81 knockdown mediated the downregulation of inflammatory cytokine interleukin-8 (IL-8). In conclusion, these findings indicate that downregulation of KRT81 could inhibit progression of melanoma by regulating IL-8. Therefore, KRT81 represents a potential therapeutic target for melanoma therapy.
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Sal-like protein 4 (SALL4) is a zinc finger transcription factor that has been reported to be aberrantly expressed in several human malignancies and identified as an oncogene. However, the potential role of SALL4 in osteosarcoma remains to be elucidated. In this study, we explored the biological functions of SALL4 in osteosarcoma. We found that SALL4 was overexpressed in osteosarcoma tissues and cell lines. Knockdown of SALL4 inhibited osteosarcoma cell proliferation, migration, and invasion in vitro. In addition, SALL4 knockdown suppressed osteosarcoma growth and metastasis in vivo. We also showed that SALL4 knockdown decreased the protein expression of Wnt3a and β-catenin in osteosarcoma cells. Taken together, our study showed that SALL4 plays an important role in regulating the proliferation, migration, and invasion of osteosarcoma cells. Thus, SALL4 may represent a potential therapeutic target in the treatment of osteosarcoma.
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Introduction: Osteosarcoma usually originates in the metaphyseal region of long bone, but may also arise in the diaphyseal of long bone. Diaphyseal osteosarcoma is a rare cases account for <10% of all osteosarcoma. In some cases two or more osteosarcoma lesions are seen in the same patient, at the same time (Synchronous osteosarcoma). It’s unusual condition of osteosarcoma, they are found at a frequency of about 1–3% osteosarcoma cases.
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Cases of unusual osteosarcoma comprising parosteal osteosarcoma, intraosseous well differentiated osteosarcoma, postradiation osteosarcoma, epithelioid osteosarcoma, and MFH-like osteosarcoma were reported. They were apparently differed from conventional osteosarcoma in the point of biologic activity and prognosis. Osteosarcoma is, therefore, considered as a heterogeneic tumor. It is important to make an exact diagnosis and to make an appropriate treatment depending on the diagnosis.
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O-glycosylation is a common protein modification. Aberrant O-glycosylation is associated with many cancers. GALNT1 is a GalNAc-transferase that initiates protein O-glycosylation. We found that GALNT1 is frequently up-regulated in hepatocellular carcinoma (HCC) and is associated with poor patient survival. Overexpression of GALNT1 increased and knockdown decreased HCC cell migration and invasion. Knockdown of GALNT1 inhibited EGF-induced migration and invasion. Knockdown of GALNT1 decreased EGFR activation and increased EGFR degradation, by decreasing EGFR O-glycosylation. This study demonstrates that down-regulation of GALNT1 is sufficient to suppress malignant phenotype of HCC cells by decreasing EGFR signaling. Thus, GALNT1 is a potential target in HCC.
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