LncRNA SLC7A11-AS1 promotes the progression of hepatocellular carcinoma by mediating KLF9 ubiquitination

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor, which seriously threatens the life of patients. LncRNA SLC7A11-AS1 was reported to be abnormally expressed in HCC. Here, the functions and relative molecular regulatory mechanism of SLC7A11-AS1 in HCC were investigated. Nude mice and HCC cells were used as the experimental subjects. Knockdown or overexpression of exogenous genes was conducted in HCC cells. RT-qPCR, IHC, and western blot were employed to evaluate the abundance of genes and proteins. e malignant behaviors were evaluated using CCK-8, clone formation, wound-healing, and Transwell. e locations of SLC7A11-AS1 and KLF9 in cells were determined by FISH and IF assays. e total m6A level was evaluated by dot-blot assay. m6A modi cation of SLC7A11-AS1 was detected using RNA MeRIP. e interactions among molecules were validated by RIP, ChIP, dual luciferase reporter assay, and co-IP. SLC7A11-AS1 was elevated apparently in HCC cells and HCC tissues from mice. SLC7A11-AS1 silencing could suppress HCC progression, which was validated in in vivo and in vitro experiments. Furthermore, METTL3 mediated m6A modi cation of SLC7A11-AS1 to elevate its expression. In addition, SLC7A11-AS1 downregulated KLF9 expression by a ecting STUB1-mediated ubiquitination degradation and KLF9 enhanced PHLPP2 expression to inactivate the AKT pathway. Eventually, rescue experiments revealed that KLF9 knockdown abolished SLC7A11-AS1 silencing-mediated suppression of HCC progression in vivo and in vitro. Our results unveiled that m6A-modi ed SLC7A11-AS1 promoted HCC progression by regulating the STUB1/KLF9/PHLPP2/AKT axis, indicating that targeting SLC7A11-AS1 might alleviate HCC progression.

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis

“…The lncRNA HClnc1 is able to induce PKM2 expression and mediates poor survival rate in HCC (191). The lncRNA SLC7A11-AS1 increases the ubiquitination of KLF9 to enhance tumorigenesis in HCC (192). The lncRNA PTOV1-AS1 overexpression modulates miR-505 expression, and it is able to stimulate sorafenib resistance in HCC (193).…”

Transcription factor KLF9 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by repressing KIAA1522

“…18 Downregulation of KLF9 expression through ubiquitination and degradation can worsen the progression of hepatocellular carcinoma. 19 The above indicates that KLF9 is widely involved in cancer progression through multiple pathways. However, less is known about the molecular pathway by which KLF9 regulates PC progression.…”