The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730000, China.
Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, China.
Biosci Rep. 2021 Sep 30;41(9). doi: 10.1042/BSR20210342.
The decreased level of miR-192-5p has been reported in several kinds of cancers, including bladder, colon, ovarian, and non-small cell lung cancer. However, the expression and function of miR-192-5p in papillary thyroid carcinoma/cancer (PTC) remains unknown.
The present study aimed to explore the function and underlying mechanism of miR-192-5p in PTC development.
PTC tissues and relative normal controls from PTC patients were collected. qRT-PCR analysis was performed to measure miR-192-5p and SH3RF3 mRNA level in PTC tissues and cell lines. CCK-8 method and FCM assay were used to test cell proliferation and apoptosis in TPC-1 cells, respectively. The abilities of cell migration and invasion were detected by wound healing and transwell assays, respectively. The protein expression was evaluated by Western blot. The interaction between miR-192-5p and Src homology 3 (SH3) domain containing ring finger 3 (SH3RF3) were confirmed by dual-luciferase reporter assay.
MiR-192-5p level was obviously decreased in PTC tissues and cell lines. Overexpression of miR-192-5p suppressed proliferation, migration, invasion, and EMT process, while induced apoptosis in TPC-1 cells. In addition, miR-192-5p negatively modulated SH3RF3 expression by binding to its 3'-untranslated region (3'UTR). Silencing SH3RF3 inhibited the migration, invasion, and EMT of TPC-1 cells. In the meantime, matrine, an alkaloid extracted from herb, exerted its anti-cancer effects in PTC cells dependent on increase in miR-192-5p expression and decrease in SH3RF3 expression.
We firstly declared that miR-192-5p played a tumor suppressive role in PTC via targeting SH3RF3. Moreover, matrine exerted its anti-cancer effects in PTC via regulating miR-192-5p/SH3RF3 pathway.
miR-192-5p 的水平降低已在多种癌症中报道，包括膀胱癌、结肠癌、卵巢癌和非小细胞肺癌。然而，miR-192-5p 在甲状腺乳头状癌/癌（PTC）中的表达和功能尚不清楚。
本研究旨在探讨 miR-192-5p 在 PTC 发展中的作用和潜在机制。
收集 PTC 患者的 PTC 组织和相对正常对照。通过 qRT-PCR 分析测量 PTC 组织和细胞系中 miR-192-5p 和 SH3RF3 mRNA 的水平。CCK-8 法和 FCM 分析分别用于检测 TPC-1 细胞的增殖和凋亡。通过划痕愈合和 Transwell 测定分别检测细胞迁移和侵袭能力。通过 Western blot 评估蛋白表达。通过双荧光素酶报告实验证实 miR-192-5p 与含 SH3 结构域的 3 型受体（SH3RF3）之间的相互作用。
miR-192-5p 的水平在 PTC 组织和细胞系中明显降低。过表达 miR-192-5p 抑制 TPC-1 细胞的增殖、迁移、侵袭和 EMT 过程，同时诱导细胞凋亡。此外，miR-192-5p 通过结合其 3'-非翻译区（3'UTR）负调控 SH3RF3 的表达。沉默 SH3RF3 抑制 TPC-1 细胞的迁移、侵袭和 EMT。同时，苦参碱，一种从草药中提取的生物碱，通过增加 miR-192-5p 的表达和降低 SH3RF3 的表达，在 PTC 细胞中发挥抗癌作用。
我们首次声明 miR-192-5p 通过靶向 SH3RF3 在 PTC 中发挥肿瘤抑制作用。此外，苦参碱通过调节 miR-192-5p/SH3RF3 通路在 PTC 中发挥抗癌作用。
