RESUMO
LINC00941 is a novel long noncoding RNA (lncRNA) and emerging as an important factor in cancer development. However, the exact function and relative regulatory mechanism of LINC00941 in carcinogenesis of esophageal squamous cell carcinoma (ESCC) remain to be further clarified. The present study was to investigate the expression level, functions, and mechanisms of LINC00941 in ESCC tumorigenesis. LINC00941 was significantly upregulated in ESCC, and upregulated LINC00941 was correlated with dismal patient outcomes. LINC00941 functioned as an oncogene by promoting cells proliferation, stemness, migration, and invasion in ESCC. In terms of mechanisms, SOX2 could bind directly to the promoter region of LINC00941 and activate its transcription. In turn, LINC00941 upregulated SOX2 through interacting with interleukin enhancer binding factor 2 (ILF2) and Y-box binding protein 1 (YBX1) at the transcriptional and post-transcriptional levels. LINC00941 recruited ILF2 and YBX1 to the promoter region of SOX2, leading to upregulation of the transcription of SOX2. Moreover, LINC00941 could promote the binding ability of ILF2 and YBX1 on mRNA of SOX2 and further stabilize SOX2 mRNA. Therefore, LINC00941 contributed to the malignant behaviors of ESCC cells via the unrestricted increase in SOX2 expression. In conclusion, our data indicate that LINC00941 exacerbates ESCC progression through forming a LINC00941-ILF2/YBX1-SOX2 positive feedback loop, and LINC00941 may be a promising prognostic and therapeutic target for ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Linhagem Celular Tumoral , MicroRNAs/genética , RNA Mensageiro/genética , Regulação Neoplásica da Expressão Gênica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismoRESUMO
BACKGROUND: Few data are available comparing homocysteine (Hcy) levels in patients with hypertension in different ethnic groups. OBJECTIVES: This study sought to determine whether there are associations of blood pressure and Hcy levels in patients with hypertension from Xinjiang Province, China. METHODS: We examined the serum total Hcy levels in a total of 451 Chinese of various ethnic groups (Han n=234 [51.9%], Uygur n=102 [22.6%], Kazak n=61 [13.5%], Hui n=54 [12.0%]) aged 18-78 years. Two groups of subjects were studied: 1) non-hypertensive, n=101; (2) hypertensive, n=350. We investigated the serum Hcy levels relationship with hypertension. RESULTS: Hcy levels of Kazak in no hypertension and hypertension patients were highest (11.9 +/- 9.8 vs 19.0 +/- 11.8 umol/L, respectively, unadjusted P=.004, adjusted P=.016). This pattern of higher Hcy values in hypertension patients was consistent across all ethnic groups even after adjustment (all P<0.05). The hypertension risks in the elevated Hcy (>13.9 umol/L) was 3.5 (95% CI, 2.2-5.4) times the normal Hcy (< or = 13.9 umol/L) (P<0.001). Even after adjustment for potential confounders, this difference remained 3.1 times higher (95% CI, 1.9-4.8) (P<.001). Bivariate correlation analysis revealed a statistically significant relationship of Hcy with systolic or diastolic blood pressure across all ethnic groups. CONCLUSION: This study confirms the existence of a significant association between hypertension and Hcy in Chinese population groups.