Knockdown of long non-coding RNA HOXD-AS1 inhibits gastric cancer cell growth via inactivating the JAK2/STAT3 pathway

• Published in: Tumor biology 2017-05, Vol.39 (5), p.1010428317705335-1010428317705335
• Main Authors: Zheng, Li, Chen, Jiangtao, Zhou, Zhongyong, He, Zhikuan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Animals; Antisense RNA; Apoptosis; Authorship; Biopsy; Breast cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Chemotherapy; Colonies; Cytokines; Enzyme inhibitors; Female; Gastric cancer; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; Genomes; Humans; Janus kinase; Janus kinase 2; Janus Kinase 2 - genetics; Kinases; Lymph nodes; Lymphatic system; Male; Medical prognosis; Metastases; Metastasis; Mice; Middle Aged; Non-coding RNA; Phosphorylation; Polymerase chain reaction; RNA, Antisense - genetics; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; Roles; Signal Transduction; Stat3 protein; STAT3 Transcription Factor - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Transcription; Tumor cell lines; Tumors; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1177/1010428317705335

Long non-coding RNA HOXD-AS1 (HOXD cluster antisense RNA 1) has been demonstrated to be closely associated with the progression of several tumors. However, the biological function of HOXD-AS1 and the underlying molecular mechanism in gastric cancer are still unclear. The expression of HOXD-AS1 in gastric cancer cell lines was evaluated by quantitative real-time polymerase chain reaction. The association of HOXD-AS1 expression and clinical parameters was statistically analyzed by chi-square test. Cell viability, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in treated SGC-7901 and BGC-823 cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and western blot analysis, respectively. The results indicated that HOXD-AS1 was significantly upregulated in gastric cancer cells and clinically involved in tumor size, invasion depth, tumor–node–metastasis stages, regional lymph nodes, lymphatic metastasis, as well as distant metastasis. HOXD-AS1 knockdown dramatically inhibited gastric cancer cell proliferation, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in vitro. In addition, HOXD-AS1 overexpression significantly promoted gastric cancer cell proliferation and colony formation capacity, whereas both Janus kinase small interfering RNAs and Janus kinase 2 inhibitor AG490 overturned these effects. Furthermore, xenograft assays confirmed the biological function of HOXD-AS1 in vivo. Taken together, our data elucidate that knockdown of HOXD-AS1 dramatically suppresses gastric cancer cell growth by inactivating the Janus kinase 2/signal transducer and activator of transcription 3 pathway in vitro and in vivo, contributing to a better understanding of gastric cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA–directed diagnosis and therapy against this disease.