Disease relevance of SEMA3B

• Loss of heterozygosity at SEMA3B or SEMA3F was demonstrated in none of the benign tumors, 8% of borderline tumors, and 29% of carcinomas [1].
• Loss of the 3p21.3-encoded semaphorins, SEMA3B and SEMA3F, is implicated in lung cancer development [2].
• Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect [3].
• Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line [4].
• We analyzed the methylation status of RASSF1A, BLU and SEMA3B in 35 hepatocellular carcinomas (HCCs) and 15 cholangiocarcinomas (CCs) by methylation-specific PCR and loss of heterozygosity (LOH) at 3p21.3 after microdissection [5].

High impact information on SEMA3B

• Research into the origins of introns is at a critical juncture in the resolution of theories on the evolution of early life (which came first, RNA or DNA?), the identity of LUCA (the last universal common ancestor, was it prokaryotic- or eukaryotic-like?), and the significance of noncoding nucleotide variation [6].
• We studied the mechanism of SEMA3B-induced tumor cell apoptosis and found that vascular endothelial growth factor (VEGF)165 significantly decreased the proapoptotic and antimitotic effect of transfected or secreted SEMA3B on lung and breast cancer cells [3].
• VEGF165 binds to neuropilin, receptors for SEMA3B, and we found that SEMA3B competed for binding of 125I-VEGF165 to lung and breast cancer cells [3].
• The common method of inactivation of SEMA3B is by allele loss and tumor-acquired promoter methylation [3].
• Semaphorins SEMA3B and its homologue SEMA3F are 3p21.3 candidate tumor suppressor genes (TSGs), the expression of which is frequently lost in lung cancers [7].

Chemical compound and disease context of SEMA3B

• Sequencing of sodium bisulfite-treated DNA showed dense methylation of CpG sites in the SEMA3B 5' region of lung cancers not expressing SEMA3B but no methylation in SEMA3B-expressing tumors [7].

Biological context of SEMA3B

• H1299 cells transfected with wild-type but not mutant SEMA3B underwent apoptosis [7].
• Colony formation of H1299 cells was reduced 90% after transfection with wild-type SEMA3B compared with the control vector [7].
• These results are consistent with SEMA3B functioning as a TSG, the expression of which is inactivated frequently in lung cancers by allele loss and promoter region methylation [7].
• By contrast, only 30-40% reduction in colony formation was seen after the transfection of SEMA3F or SEMA3B variants carrying lung cancer-associated single amino acid missense mutations [7].
• The presence of hypermethylation was statistically associated with LOH of SEMA3B and correlated with downregulation of mRNA transcripts [5].

Anatomical context of SEMA3B

• The presence of hypermethylation was statistically associated with loss of SEMA3B expression in both cell lines (P = 0.02) and primary tumors (P < 0.01) [8].

Associations of SEMA3B with chemical compounds

• Treatment with 5-AZAC restored SEMA3B expression in NSCLC cell line [8].

Other interactions of SEMA3B

• In conclusion, we hypothesize that VEGF165, produced by tumor cells, acts as an autocrine survival factor and that SEMA3B mediates its tumor-suppressing effects, at least in part, by blocking this VEGF autocrine activity [3].
• Previously, the RASSF1A, BLU and SEMAPHORIN 3B (SEMA3B) candidate tumor suppressor genes on chromosome 3p21.3 were found to be inactivated and downregulated by genetic and epigenetic changes in lung cancer [5].
• Alterations in 3p tumor suppression genes (TSGs) appear especially early, including those of RASSF1A and SEMA3B at 3p21.3, followed by changes in 9p (p16), 8p, and then multiple other sites [9].
• In addition, some genes were up-regulated, including matrix metalloproteinse 2(MMP-2), MMP-16(MT3-MMP), SKY, CD9 and semaphorin V [10].

Analytical, diagnostic and therapeutic context of SEMA3B

• Applying quantitative methylation specific PCR (QMSP) we analyzed bronchial aspirates from 75 patients with primary lung cancer and 64 bronchial aspirates of patients diagnosed with benign lung disease for promoter methylation of 3 candidate marker genes (p16(INK4a), RARB2 and SEMA3B) [11].

References