Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression.
Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression.
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假基因 PTENP1 作为竞争性内源性 RNA 抑制透明细胞肾细胞癌进展
DOI：
10.1158/1535-7163.mct-14-0245
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发表时间：
2014-12
影响因子：
5.7
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Yu G;Yao W;Gumireddy K;Li A;Wang J;Xiao W;Chen K;Xiao H;Li H;Tang K;Ye Z;Huang Q;Xu H
PTENP1是PTEN肿瘤抑制基因(TSG)的假基因。PTENP1在肾透明细胞癌(CcRCC)中的作用尚未研究。我们发现PTENP1在肾细胞癌组织和细胞中由于甲基化而下调。PTENP1和PTEN是miRNA miR21的直接靶点，miR21可抑制其在肾癌细胞系中的表达。MiR21的表达在体外可促进肾癌细胞的增殖、迁移、侵袭，在体内可促进肿瘤的生长和转移。在表达miR21的细胞中过表达PTENP1可以减少细胞的增殖、侵袭、肿瘤生长和转移，概括了PTEN表达所诱导的表型。在体外和体内，PTENP1在ccRCC细胞中的过表达使这些细胞对顺铂和吉西他滨治疗敏感。在临床标本中，PTENP1和PTEN的表达呈正相关，两者与miR21的表达呈负相关。PTENP1不表达的肾细胞癌患者生存率较低。这些结果表明，PTENP1在ccRCC中作为竞争内源性RNA(CENA)发挥作用，以抑制癌症进展。
PTENP1 is a pseudogene of the PTEN tumor suppression gene (TSG). The functions of PTENP1 in clear-cell renal cell carcinoma (ccRCC) have not yet been studied. We found that PTENP1 is downregulated in ccRCC tissues and cells due to methylation. PTENP1 and PTEN are direct targets of miRNA miR21 and their expression is suppressed by miR21 in ccRCC cell lines. miR21 expression promotes ccRCC cell proliferation, migration, invasion in vitro, and tumor growth and metastasis in vivo. Overexpression of PTENP1 in cells expressing miR21 reduces cell proliferation, invasion, tumor growth, and metastasis, recapitulating the phenotypes induced by PTEN expression. Overexpression of PTENP1 in ccRCC cells sensitizes these cells to cisplatin and gemcitabine treatments in vitro and in vivo. In clinical samples, the expression of PTENP1 and PTEN is correlated, and both expressions are inversely correlated with miR21 expression. Patients with ccRCC with no PTENP1 expression have a lower survival rate. These results suggest that PTENP1 functions as a competing endogenous RNA (ceRNA) in ccRCC to suppress cancer progression.