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Long noncoding RNA CASC9 promotes the proliferation and metastasis of papillary thyroid cancer via sponging miR‐488‐3p

机译:较长的非编码RNA CASC9通过使miR‐488‐3p变海绵促进甲状腺乳头状癌的增殖和转移

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摘要

Cancer susceptibility candidate 9 (CASC9) is a recently identified lncRNA that acted as a tumor promotor in diversified cancer types. However, its role in papillary thyroid cancer (PTC) remains unknown. The expression of CASC9 was measured in 52 human PTC tissues and PTC cell lines as well as their controls. The proliferation, migration, and invasion of PTC cells were determined after knockdown or overexpression of CASC9 to evaluate the effect of CASC9 on PTC cells. Also, the role of PTC tumorigenesis was confirmed in mice xenograft models. Additionally, the underlying mechanisms of CASC9 were further researched. We found that CASC9 expression was augmented in human PTC tissues and cells. Higher CASC9 expression was associated with large tumor size, advanced stage, or lymph node metastasis. Downregulation of CASC9 significantly attenuated the proliferative, migrative, and invasive abilities of PTC cells, and suppressed tumorigenesis in vivo. While overexpression of CASC9 elevated the proliferation, migration, and invasion of PTC cells. miR‐488‐3p expression was decreased, and ADAM9 level was increased in PTC tissues and cells. CASC9 expression was negatively related to miR‐488‐3p, but positively associated with ADAM9 expression in PTC tissues. Molecular mechanism analysis revealed that CASC9 functioned via sponging miR‐488‐3p to regulate ADAM9 expression, followed by activation of EGFR‐Akt signaling. In conclusion, lncRNA CASC9 promoted the malignant phenotypes of PTC via modulating miR‐488‐3p/ADAM9 pathway. This study may provide a novel therapeutic target for the treatment of PTC.
机译:癌症易感候选物9(CASC9)是最近鉴定出的lncRNA,可在多种癌症类型中充当肿瘤促进剂。然而,其在甲状腺乳头状癌(PTC)中的作用仍然未知。在52个人PTC组织和PTC细胞系以及它们的对照中测量了CASC9的表达。敲除或过度表达CASC9后,测定PTC细胞的增殖,迁移和侵袭,以评估CASC9对PTC细胞的影响。同样,在小鼠异种移植模型中证实了PTC肿瘤发生的作用。此外,进一步研究了CASC9的潜在机制。我们发现CASC9表达在人PTC组织和细胞中增加。 CASC9的较高表达与肿瘤大,晚期或淋巴结转移有关。 CASC9的下调显着减弱了PTC细胞的增殖,迁移和侵袭能力,并抑制了体内肿瘤发生。虽然CASC9的过表达提高了PTC细胞的增殖,迁移和侵袭。在PTC组织和细胞中,miR‐488‐3p表达降低,ADAM9水平升高。 CASC9表达与miR-488-3p呈负相关,但与PTC组织中的ADAM9表达呈正相关。分子机理分析表明,CASC9通过使miR-488-3p海绵化来调节ADAM9的表达,然后激活EGFR-Akt信号传导。总之,lncRNA CASC9通过调节miR-488-3p / ADAM9途径促进了PTC的恶性表型。这项研究可能为PTC的治疗提供一个新的治疗目标。

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