title: Limb-bud and Heart (LBH) functions as a tumor suppressor of nasopharyngeal carcinoma by inducing G1/S cell cycle arrest.
abstract: Epstein-Barr virus-encoded latent membrane protein-1 (LMP1) plays a fundamental role in the malignant transformation of nasopharyngeal carcinoma (NPC), although the mechanism is not well understood. Here, we showed that Limb-bud and Heart (LBH) is considerably downregulated in patient NPC tissues. The expression of LBH in biopsies of 40 consecutive NPC patients devoid of initial distant metastasis and treated according to consistent guidelines was also analyzed, and we found the LBH expression level was correlated with some of clinicopathological features, disease-specific survival (DSS), distant metastasis-free survival (DMFS). We further determined that LBH normally induces NPC cell cycle arrest at the G1/S transition, and LBH can suppress the growth of transplanted NPC tumors in vivo by downregulating LMP1-mediated NF-κB transcriptional activity. Transforming growth factor-beta 1 (TGF-β1) normally protects against tumor development by suppressing cell proliferation, but NPC cells acquire resistance to TGF-β1-mediated inhibition. We found that TGF-β1 inhibits NF-κB transcriptional activity and nasopharyngeal epithelial cell proliferation through upregulating LBH expression. These data reveal a previously unknown NPC transformation mechanism and provide a new concept and treatment strategy for LMP1-driven oncogenesis in NPC.
authors.affiliation: Experimental Medical Research Center, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Qicai
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Guan
authors.affiliation: 1] Experimental Medical Research Center, Guangzhou Medical University, Guangzhou 510182, China [2] Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangzhou 510060, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510089, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Experimental Medical Research Center, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangzhou 510060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000187:drug effects; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C531176:LBH protein, human; D016328:NF-kappa B; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014763:Viral Matrix Proteins