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RABL6 高表达促进食管鳞癌细胞增殖并预测不良预后。

High expression of RABL6 promotes cell proliferation and predicts poor prognosis in esophageal squamous cell carcinoma.

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.

Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.

出版信息

BMC Cancer. 2020 Jun 29;20(1):602. doi: 10.1186/s12885-020-07068-w.

Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is a common malignant carcinoma of digestive system with high mortality. RAB, member RAS oncogene family like 6 (RABL6), a member of the RAS subfamily, has been reported as an important molecule in several cancers. However, its potential role in ESCC still remains unclear.

METHODS

RABL6 mRNA expression was detected in 93 frozen ESCC samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Immunohistochemistry was applied to evaluate the RABL6 expression in tissue microarray containing 171 pairs of ESCC tissues and paired para-cancerous tissues. We evaluated RABL6 expression and its correlation with clinicopathological characteristics and survival. Subsequently, the impact of RABL6 knockdown on the ability of cell proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT) of ESCC cells was investigated by MTS, Focus formation, flow cytometry, Transwell assays, qRT-PCR, western blot, inverted microscope observation and phalloidin staining, respectively.

RESULTS

Compared to paired para-cancerous tissues, RABL6 was highly expressed in ESCC. The RABL6 high-expression was associated with worse prognosis. We also revealed silencing of RABL6 caused inhibition of cell proliferation, invasion and migration. Further experiments demonstrated that knockdown of RABL6 suppressed the aggressive biological activities of ESCC by suppressing EMT in ESCC cells.

CONCLUSIONS

RABL6 functions as a tumor oncogene in ESCC. It would be a potential biomarker predicting prognosis, and a novelty target for ESCC therapy.

摘要

背景

食管鳞状细胞癌(ESCC)是一种常见的消化系统恶性癌,死亡率较高。RAB,RAS 癌基因家族成员 6(RABL6),RAS 亚家族的成员,已被报道为几种癌症中的重要分子。然而,其在 ESCC 中的潜在作用尚不清楚。

方法

采用实时定量逆转录聚合酶链反应(qRT-PCR)检测 93 例冷冻 ESCC 样本中 RABL6mRNA 的表达。应用免疫组织化学法检测组织微阵列中 171 对 ESCC 组织及其配对癌旁组织中 RABL6 的表达。我们评估了 RABL6 的表达及其与临床病理特征和生存的相关性。随后,通过 MTS、焦点形成、流式细胞术、Transwell 检测、qRT-PCR、Western blot、倒置显微镜观察和鬼笔环肽染色分别研究了 RABL6 敲低对 ESCC 细胞增殖、凋亡、迁移和上皮间质转化(EMT)能力的影响。

结果

与配对癌旁组织相比,RABL6 在 ESCC 中高表达。RABL6 高表达与预后不良相关。我们还发现 RABL6 沉默导致 ESCC 细胞增殖、侵袭和迁移受到抑制。进一步的实验表明,RABL6 的敲低通过抑制 EMT 抑制了 ESCC 细胞的侵袭性生物学活性。

结论

RABL6 在 ESCC 中作为肿瘤癌基因发挥作用。它可能成为预测预后的潜在生物标志物,也是 ESCC 治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d8e/7325041/2b53e5966b40/12885_2020_7068_Fig1_HTML.jpg

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