Background:N6-methyladenosine(m6A)RNA modification has been demonstrated to be a significant regulatory process in the progression of various tumors,including breast cancer.Fat mass and obesity-associated(FTO)enzyme,i...Background:N6-methyladenosine(m6A)RNA modification has been demonstrated to be a significant regulatory process in the progression of various tumors,including breast cancer.Fat mass and obesity-associated(FTO)enzyme,initially known as the obesity-related protein,is the first identified m6A demethylase.However,the relationship between FTO and breast cancer remains controversial.In this study,we aimed to elucidate the role and clinical significance of FTO in breast cancer and to explore the underlying mechanism.Methods:We first investigated the expression of FTO in breast cancer cell lines and tissues by quantitative reverse transcription-PCR(qRT-PCR),Western blotting,and immunohistochemistry.Wound healing assay and Transwell assay were performed to determine the migration and invasion abilities of SKBR3 and MDAMB453 cells with either knockdown or overexpression of FTO.RNA sequencing(RNA-seq)was conducted to decipher the downstream targets of FTO.qRT-PCR,luciferase reporter assay,and Western blotting were employed to confirm the existence of the FTO/miR-181b-3p/ARL5B axis.The biological function of ADP ribosylation factor like GTPase 5B(ARL5B)in breast cancer cells was evaluated by wound healing assay and Transwell invasion assay.Results:High FTO expression was observed in human epidermal growth factor receptor 2(HER2)-positive breast cancer,predicting advanced progression(tumor size[P<0.001],nuclear grade[P=0.001],peritumoral lymphovascular invasion[P<0.001),lymph node metastasis[P=0.002],and TNM stage[P=0.001])and poor prognosis.Moreover,FTO promoted cell invasion and migration in vitro.Mechanistically,RNA-seq and further confirmation studies suggested that FTO up-regulated ARL5B by inhibiting miR-181b-3p.We further verified that ARL5B also displayed carcinogenic activity in breast cancer cells.Conclusion:Our work demonstrated the carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.展开更多
目的探讨超声引导下穿刺活检(ultrasound-guided core needle biopsy,US-CNB)对乳腺病变超声诊断图像的影像报告与数据系统(breast imaging reporting and data system,BI-RADS)分级弹性校正4B类结节在乳腺癌定性诊断中的临床应用价值...目的探讨超声引导下穿刺活检(ultrasound-guided core needle biopsy,US-CNB)对乳腺病变超声诊断图像的影像报告与数据系统(breast imaging reporting and data system,BI-RADS)分级弹性校正4B类结节在乳腺癌定性诊断中的临床应用价值。方法选取2014年9月至2016年9月93例就诊于本院且经乳腺超声常规检查后弹性校正分级为BI-RADS 4B类结节的患者,测算评估后行US-CNB,以术后病理结果为金标准,分析其诊断特异度、灵敏度、准确率、假阴性率,并比较其与术后病理诊断结果的符合率。结果 93例患者US-CNB的结果中55例为乳腺癌,38例为良性肿物,术后病理结果中58例为乳腺癌,35例为良性肿物。55例US-CNB结果为乳腺癌者与术后病理一致,38例US-CNB结果为良性结节者中3例术前US-CNB分别报告为硬化性腺病与纤维腺瘤而术后病理类型为浸润性导管癌、浸润性乳头癌和化生性癌。US-CNB诊断乳腺癌的特异度为100%,灵敏度为94.82%,准确率为96.77%,假阴性率为5.17%。结论 US-CNB联合BI-RADS分级弹性校正对乳腺4B类单发结节的诊断特异度、灵敏度及准确率较高,作为一种精准的诊疗技术为临床制定后续治疗方案以及预后判断提供了准确的病理依据与重要信息。展开更多
文摘目的探讨B超引导下Mammotome微创旋切系统对乳腺肿块诊断与治疗的应用价值.方法132例221处乳腺肿块在B超引导下进行Mammotome微创旋切术.其中一侧单发肿块79例,单侧或双侧多发肿块53例,直径0.5～5.2cm,平均1.4 cm,149处肿块临床可扪及.结果所有肿块均完成Mammotome微创旋切切除,平均旋切24次,平均36 min (10～40 min).无一例操作失败.所有肿块均获得明确病理诊断,良性病变129例,乳腺浸润性导管癌3例均行乳腺癌改良根治术.皮肤伤口小,除10例有轻度皮下瘀血外无其它并发症.结论B超引导Mammotome微创旋切系统进行乳腺肿块切除,操作简易,切除彻底,创伤小.
文摘Background:N6-methyladenosine(m6A)RNA modification has been demonstrated to be a significant regulatory process in the progression of various tumors,including breast cancer.Fat mass and obesity-associated(FTO)enzyme,initially known as the obesity-related protein,is the first identified m6A demethylase.However,the relationship between FTO and breast cancer remains controversial.In this study,we aimed to elucidate the role and clinical significance of FTO in breast cancer and to explore the underlying mechanism.Methods:We first investigated the expression of FTO in breast cancer cell lines and tissues by quantitative reverse transcription-PCR(qRT-PCR),Western blotting,and immunohistochemistry.Wound healing assay and Transwell assay were performed to determine the migration and invasion abilities of SKBR3 and MDAMB453 cells with either knockdown or overexpression of FTO.RNA sequencing(RNA-seq)was conducted to decipher the downstream targets of FTO.qRT-PCR,luciferase reporter assay,and Western blotting were employed to confirm the existence of the FTO/miR-181b-3p/ARL5B axis.The biological function of ADP ribosylation factor like GTPase 5B(ARL5B)in breast cancer cells was evaluated by wound healing assay and Transwell invasion assay.Results:High FTO expression was observed in human epidermal growth factor receptor 2(HER2)-positive breast cancer,predicting advanced progression(tumor size[P<0.001],nuclear grade[P=0.001],peritumoral lymphovascular invasion[P<0.001),lymph node metastasis[P=0.002],and TNM stage[P=0.001])and poor prognosis.Moreover,FTO promoted cell invasion and migration in vitro.Mechanistically,RNA-seq and further confirmation studies suggested that FTO up-regulated ARL5B by inhibiting miR-181b-3p.We further verified that ARL5B also displayed carcinogenic activity in breast cancer cells.Conclusion:Our work demonstrated the carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.
