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Background: Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality. The long‐term use of sorafenib, a targeted drug for hepatocellular carcinoma, will lead to drug resistance, and patients are prone to cancer metastasis, the molecular mechanism of which is still unclear. Methods: In our study, we constructed a sorafenib‐resistant hepatocellular carcinoma cell line (HepG2/Sora) and validated the resistance in vivo and in vitro. Transwell assays confirmed the invasion and migration abilities of cells. Colorimetric assays confirmed that the level of m6A methylation modification in cells. RT‐qPCR and Western blot assays confirmed that the expression levels of KIAA1429 in HepG2/Sora cells and tissues. The EMT related proteins were detected by Western blot assay. Results: Transwell and Western blot assays confirmed that HepG2/Sora cells had higher invasion and migration abilities and showed EMT phenomena. Colorimetric assays confirmed that the level of m6A methylation modification was upregulated in HepG2/Sora cells. Transwell and Western blot assays confirmed that inhibiting m6A methylation in HepG2/Sora cells inhibited their invasion, migration ability and EMT phenomenon. RT‐qPCR and Western blot assays confirmed that the expression levels of KIAA1429 in HepG2/Sora cells and tissues was increased. Silencing KIAA1429 in HepG2/Sora cells inhibited their invasion, migration ability and EMT phenomenon. Finally, we found that the medium supernatant of sorafenib‐resistant HepG2/Sora cells induced vascular production of EA.hy926 cells, and silencing KIAA1429 inhibited this induction effect. Conclusion: We suggest that KIAA1429 promotes sorafenib‐resistant hepatocellular carcinoma invasion, migration and EMT by mediating m6A methylation. KIAA1429 with its mediated m6A methylation may be a key factor for sorafenib‐resistant patients prone to cancer cell metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Most cancer cells perform glycolysis despite having sufficient oxygen. The specific metabolic pathways of cancer cells have become the focus of cancer treatment. Recently, accumulating evidence indicates oxidative phosphorylation (OXPHOS) and glycolysis can be regulated with each other. Thus, we suggest that the glycolysis of cancer cells is inhibited by restoring or improving OXPHOS in cancer cells. In our study, we found that oxaloacetate (OA) induced apoptosis in HepG2 cells in vivo and in vitro. Meanwhile, we found that OA induced a decrease in the energy metabolism of HepG2 cells. Further results showed that the expression and activity of glycolytic enzymes were decreased with OA treatment. Conversely, the expression and activity of enzymes involved in the TCA cycle and OXPHOS were increased with OA treatment. The results indicate that OA can inhibit glycolysis through enhancement of OXPHOS. In addition, OA‐mediated suppression of HIF1α, p‐Akt, and c‐myc led to a decrease in glycolysis level. Therefore, OA has the potential to be a novel anticancer drug. [ABSTRACT FROM AUTHOR]