BackgroundEmerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 and we still know little about its expressions, roles and mechanisms.MethodsRACE was used to obtain the sequence of ZEB1-AS1. RNA interference was used to decrease ZEB1-AS1 expression. Adenovirus expression vector was used to increase ZEB1-AS1 expression. CHIP and RIP were used to detect the epigenetic mechanisms by which ZEB1-AS1 regulated ZEB1. CCK8 assay, wound healing assay and transwell assay were used to measure proliferation and migration of prostate cancer cells.ResultsIn this study, in prostate cancer cells, we found that RNAi-mediated downregulation of ZEB1-AS1 induced significant ZEB1 inhibition while artificial overexpression of ZEB1-AS1 rescued ZEB1 expression, which means that ZEB1-AS1 promotes ZEB1 expression. Also, ZEB1-AS1 indirectly inhibited miR200c, the well-known target of ZEB1, and upregulated miR200c’s target BMI1. Mechanistically, ZEB1-AS1 bound and recruited histone methyltransferase MLL1 to the promoter region of ZEB1, induced H3K4me3 modification therein, and activated ZEB1 transcription. Biologically, ZEB1-AS1 promoted proliferation and migration of prostate cancer cells.ConclusionsCollectively, ZEB1-AS1 functions as an oncogene in prostate cancer via epigenetically activating ZEB1 and indirectly regulating downstream molecules of ZEB1.
Surgery after CCRT for advanced cervical cancer enabled evaluation of the pathologic response to therapy, improved local disease control in patients with a partial pathologic response, and enhanced survival. The most appropriate surgical approach was extrafascial hysterectomy with pelvic lymph node dissection.
BackgroundTo study the distribution pattern of lymph node metastases of stage IA to IIA cervical cancer and to clarify the individualized clinical target volume delineation of regional lymph nodes (CTVn).MethodsA total of 665 cases with International Federation Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The clinicopathological factors related to lymph node metastases were analyzed using logistic regression analysis.ResultsPelvic lymph node metastases were found in 168 of 665 patients resulting in a metastasis rate of 25.3%. Binary logistic regression analysis showed that age, lymph vascular space involvement, and deep stromal invasion statistically influenced pelvic lymph node metastases (p = 0.017, < 0.001, < 0.001, respectively). Pathological morphology type, lymph node metastases of the obturator, the external iliac and internal iliac, and the para-aortic had a strong influence on lymph node metastases of the common iliac (p = 0.022, 0.003, < 0.001, 0.009, respectively). Tumor size and lymph node metastases of the common iliac were significantly related to lymph node metastases of the para-aortic (p = 0.045, < 0.001, respectively). Lymph node metastases of the obturator, the external iliac and internal iliac were strongly correlated to lymph node metastases of the circumflex iliac node distal to the external iliac node (CINDEIN; p = 0.027, 0.024, respectively).ConclusionsFactors related to lymph node metastases should be comprehensively considered to design and tailor CTVn for radiotherapy of cervical cancer. Selective regional irradiation including the correlated lymphatic drainage regions should be performed.
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