Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1.

Abstract

Development of novel targeted therapy holds promise for conquering chemotherapy resistance, one of major hurdles in current liver cancer treatment. We found that long non-coding RNA TUC338 is involved in the development of hepatocellular carcinoma (HCC) and sorafenib resistance. HCC cell lines were transfected with siTUC338, then cell proliferation and invasion ability were investigated by MTT and Transwell assay. Sorafenib resistance HepG2 cells were generated to test the role of TUC338 in sorafenib sensitivity. Intratumoral delivering of siTUC338 was used to analyze the sorafenib treatment response in HepG2/Sor xenografts in vivo. Higher levels of TUC338 were found both in HCC tissues and cell lines, knockdown of TUC338 was accompanied with increased expression of RASAL1 in HCC cell line with increased proliferation and invasion ability, knockdown of TUC338 could activate the RASAL1 pathway and inhibit tumor growth genes by directly targeting RASAL1 3'-UTR. Furthermore, knockdown of TUC338 in HepG2 sorafenib sensitized its reaction to the treatment of sorafenib, which was accompanied by increased expression RASAL1; intratumoral delivering of siTUC338 could also restore sorafenib treatment response in HepG2/Sor xenografts in vivo. These findings provide direct evidence that the TUC338/RASAL1 axis might play an essential role in sorafenib-resistance of liver cancer cells, suggesting the signaling cohort could serve as a novel therapeutic target for the treatment of chemotherapy resistant liver cancer.

• Authors: Weidong Jin, Lei Chen, Xun Cai, Yunxiao Zhang, Jianxin Zhang, Dangdang Ma, Xiong Cai, Tao Fu, Zhengping Yu, Fuxiang Yu, Gang Chen
• Journal: Oncology reports (Oncol Rep) Vol. 37 Issue 1 Pg. 273-280 (Jan 2017) ISSN: 1791-2431 [Electronic] Greece
• PMID: 27878301 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• GTPase-Activating Proteins
• Phenylurea Compounds
• RASAL1 protein, human
• RNA, Long Noncoding
• long non-coding RNA TUC338, human
• Niacinamide
• Sorafenib

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Carcinoma, Hepatocellular (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Drug Resistance, Neoplasm (drug effects, genetics)
• GTPase-Activating Proteins (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Liver Neoplasms (drug therapy, genetics, pathology)
• Male
• Mice, Nude
• Niacinamide (analogs & derivatives, pharmacology)
• Phenylurea Compounds (pharmacology)
• RNA, Long Noncoding (genetics)
• Sorafenib
• Xenograft Model Antitumor Assays