Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261041, P.R. China.
Department of Emergency, Weifang Traditional Chinese Hospital, Weifang, Shandong 261041, P.R. China.
Mol Med Rep. 2018 Jun;17(6):7521-7528. doi: 10.3892/mmr.2018.8856. Epub 2018 Apr 5.
The incidence of thyroid cancer has increased the past few decades, the most frequent type has been identified to be the papillary thyroid carcinoma (PTC). Following thyroidectomy, radioiodine ablation treatment on PTC is routinely performed. However, many patients do not benefit from radioiodine therapy. Therefore, novel targeted therapies to suppress tumor growth and improve radioiodine uptake are required. La ribonucleoprotein domain family member (LARP)7 is a member of the LARP family and functions as a potential suppressor of the progression of carcinoma. In the present study, the expression status of LARP7 in PTC tissues and cell lines was investigated, and the cell viability, proliferation and apoptotic rate, radioiodine uptake ability of PTC cells with overexpression of LARP7 in vitro was determined. Expression levels of LARP7 were significantly downregulated in PTC tissues and cell lines. Overexpression of LARP7 inhibited the proliferation and increased the radioiodine uptake ability of PTC cells in vitro and inhibited the tumor growth in vivo. Furthermore, LARP7 overexpression inhibited the sonic hedgehog (SHH) signaling pathway and increased sodium/iodide symporter (NIS) expression. However, treatment with recombinant human SHH partially reduced radioiodine uptake ability and NIS expression induced by LARP7. In conclusion, LARP7 may act as a tumor suppressor in PTC by inhibiting the SHH signaling pathway and may be a promising therapeutic target in patients with PTC.
在过去几十年中，甲状腺癌的发病率有所增加，最常见的类型已被确定为甲状腺乳头状癌（PTC）。在甲状腺切除术后，通常对 PTC 进行放射性碘消融治疗。然而，许多患者并未从放射性碘治疗中受益。因此，需要新型的靶向疗法来抑制肿瘤生长并提高放射性碘摄取率。核蛋白体 RNA 结合蛋白家族成员（LARP）7 是 LARP 家族的成员，作为癌进展的潜在抑制剂发挥作用。在本研究中，研究了 LARP7 在 PTC 组织和细胞系中的表达状态，并确定了体外过表达 LARP7 对 PTC 细胞活力、增殖和凋亡率以及放射性碘摄取能力的影响。LARP7 的表达水平在 PTC 组织和细胞系中明显下调。过表达 LARP7 抑制了 PTC 细胞的增殖并增加了其放射性碘摄取能力，并抑制了体内肿瘤生长。此外，LARP7 过表达抑制了 sonic hedgehog（SHH）信号通路并增加了钠/碘转运体（NIS）的表达。然而，用重组人 SHH 处理部分降低了 LARP7 诱导的放射性碘摄取能力和 NIS 表达。总之，LARP7 可能通过抑制 SHH 信号通路在 PTC 中起肿瘤抑制作用，并且可能成为 PTC 患者有前途的治疗靶点。
