HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p (Publication with Expression of Concern. See vol. 77, pg. 495, 2021) (Retracted Article)
HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p (Publication with Expression of Concern. See vol. 77, pg. 495, 2021) (Retracted Article)
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DOI：
10.1007/s13105-019-00669-5
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发表时间：
2019-06-01
影响因子：
3.4
通讯作者：
Su, Haiying
中科院分区：
文献类型：
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作者：
Chu, Ping;Xu, Lina;Su, Haiying
据报道，肝癌中高度上调的异常表达（HULC）参与卵巢癌的发展。最近的一项研究表明，hulc调节的microRNAs （miRNAs）在肿瘤发生过程中起作用。为了证实HULC在卵巢肿瘤发生中的作用，我们探讨了HULC表达对卵巢癌细胞发育的影响及其机制。我们用pEX-HULC、sh-HULC和miR-125a-3p模拟物及其相应的阴性对照（pEX-3、sh-NC和NC）转染SKOV3细胞，改变HULC和miR-125a-3p的表达，并通过定量反转录PCR （qRT-PCR）分析结果。Western blot检测细胞周期、凋亡和信号通路相关蛋白的表达。分别采用溴脱氧尿苷（BrdU）掺入法、膜联蛋白v -异硫氰酸荧光素(FITC)/碘化丙啶（PI）法和跨井迁移和侵袭法研究细胞的增殖、凋亡、迁移和侵袭。HULC过表达促进SKOV3细胞的增殖、迁移和侵袭，抑制SKOV3细胞的凋亡。此外，HULC负向调节miR-125a-3p的表达。此外，miR-125a-3p模拟物逆转了HULC对SKOV3细胞增殖、迁移、侵袭和凋亡的影响。此外，我们发现HULC通过下调miR-125a-3p的表达，增强了磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶点（PI3K/AKT/mTOR）信号通路中调控因子的磷酸化表达。HULC过表达通过下调miR-125a-3p激活PI3K/AKT/mTOR信号通路，促进卵巢癌的发展。
The aberrant expression of highly upregulated in liver cancer (HULC) has been reported to participate in ovarian cancer development. A recent research has revealed that HULC-modulated microRNAs (miRNAs) in tumorigenesis. To confirm the functions of HULC on tumorigenesis of ovarian, we explored the effects of HULC expression on ovarian cancer cell development, as well as the underlying mechanism. We transfected SKOV3 cells with pEX-HULC, sh-HULC, and miR-125a-3p mimic as well as their corresponding negative controls (pEX-3, sh-NC, and NC) to alter the expression of HULC and miR-125a-3p, which were analyzed by quantitative reverse transcription PCR (qRT-PCR). Expression of proteins associated with cell cycle, apoptosis, and signaling pathways was determined by Western blot assay. The proliferation, apoptosis, migration, and invasion were explored by bromodeoxyuridine (BrdU) incorporation assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) method, and transwell migration and invasion assays, respectively. HULC overexpression promoted proliferation, migration, and invasion, while inhibited apoptosis of SKOV3 cells. In addition, HULC negatively regulated the expression of miR-125a-3p. Besides, miR-125a-3p mimic reversed the effects of HULC on proliferation, migration, and invasion as well as apoptosis of SKOV3 cells. Moreover, we found that HULC enhanced phosphorylated expression of regulatory factors in phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of rapamycin (PI3K/AKT/mTOR) signaling pathway by downregulating expression of miR-125a-3p. Overexpression of HULC promoted ovarian carcinoma development by activating PI3K/AKT/mTOR signaling pathway via downregulating miR-125a-3p.