LncRNA SNHG3 Promotes Hepatocellular Tumorigenesis by Targeting miR-326

LncRNA SNHG3 Promotes Hepatocellular Tumorigenesis by Targeting miR-326

QIAN ZHAO,¹ CHENSI WU,¹ JINGWEN WANG,¹ XIDONG LI,¹ YUCHEN FAN,^1,2 SHUAI GAO^1,2 and KAI WANG^1,2

¹Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China
²Institute of Hepatology, Shandong University, Jinan, Shandong, China

Small nucleolar RNA host gene 3 (SNHG3), a long noncoding RNA (lncRNA), acts as an oncogene in hepatocellular carcinoma (HCC), whereas microRNA (miR)-326 plays an inhibitory role in some types of human cancers, including melanoma, osteosarcoma, and gastric cancer. In the present study, by analyzing 47 tissue specimens of human HCC, we found that the relative expression levels of SNHG3 were significantly higher in HCC tissues than those in the adjacent noncancerous tissues, whereas the relative expression levels of miR-326 were significantly lower in HCC tissues. Furthermore, the relative mRNA levels of Sma and Mad Related Family 3 (SMAD3) and zinc finger E-box binding homeobox 1 (ZEB1) were significantly higher in HCC tissues compared with the adjacent noncancerous tissues. In human HCC cell lines, SNHG3 overexpression promoted the proliferation, migration, and epithelial-mesenchymal transition and inhibited apoptosis, whereas knockdown of SNHG3 expression exerted the opposite effects. Importantly, miR-326 or miR-326 inhibitor restored the aforementioned effects of SNHG3 overexpression or SNHG3 knockdown. We thus found that the miR-326-response element is present in SNHG3 and the 3'-untranslated region of SMAD3 mRNA. In fact, SNHG3 overexpression increased the expression levels of SMAD3 and ZEB1, while miR-326 decreased the expression levels of SMAD3. These results suggest that SNHG3 may function as a competing endogenous RNA (ceRNA) for miR-326, which in turn enhances SMAD3 and ZEB1 expression. In conclusion, we propose that SNHG3 promotes HCC progression via the miR-326/SMAD3/ZEB1 signaling pathway. The findings may provide novel targets for the diagnosis and treatment of HCC.

Keywords —— hepatocellular carcinoma; long noncoding RNA; miR-326; Sma and Mad Related Family 3; zinc finger E-box binding homeobox 1

===============================

Tohoku J. Exp. Med., 2019, 249, 43-56

Correspondence: Kai Wang, M.D., Ph.D., Department of Hepatology, Qilu Hospital of Shandong University and Institute of Hepatology, Shandong University, 107# Wenhuaxi Road, Jinan, Shandong 250012, China.

e-mail: wangdoc876@126.com; wangdoc2010@163.com