Drug resistance is a big obstacle for clinical anti-tumor treatment outcome. However, the role of HOTAIR in drug resistance in gastric cancer (GC) remains unknown. In this study, we showed that overexpression of HOTAIR enhanced paclitaxel and doxorubicin resistance in GC cells. Furthermore, the expression of HOTAIR was upregulated in GC tissues and higher expression of HOTAIR was associated with late stage. In addition, we showed that miR-217 expression was lower in GC tissues compared with the paired non-tumour tissues and downregulated expression of miR-217 was correlated with late stage. Interestingly, the expression of miR-217 was negatively correlated with HOTAIR expression in GC tissues. Ectopic expression of HOTAIR increased GC cell proliferation, cell cycle, and migration. Elevated expression of HOTAIR suppressed miR-217 expression and enhanced GPC5 and PTPN14 expression. Furthermore, we demonstrated that overexpression of miR-217 suppressed paclitaxel and doxorubicin resistance in GC cells. Ectopic expression of HOTAIR promoted drug resistance and increased GC cell proliferation, cell cycle, and migration by targeting miR-217. These data suggested that overexpression of HOTAIR enhanced paclitaxel and doxorubicin resistance in GC cells through inhibiting miR-217 expression.

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Tumor cells use metabolic reprogramming to keep up with the need for bioenergy, biosynthesis, and oxidation balance needed for rapid tumor division. This phenomenon is considered a marker of tumors, including colon cancer (CRC). As an important pathway of cellular energy metabolism, fatty acid metabolism plays an important role in cellular energy supply and oxidation balance, but presently, our understanding of the exact role of fatty acid metabolism in CRC is limited. Currently, no lipid metabolism therapy is available for the treatment of CRC. The establishment of a lipidmetabolism model regulated by oncogenes/tumor suppressor genes and associated with the clinical characteristics of CRC is necessary to further understand the mechanism of fatty acid metabolism in CRC. In this study, through multi-data combined with bioinformatic analysis and basic experiments, we introduced a tumor suppressor gene, EPHX2, which is rarely reported in CRC, and confirmed that its inhibitory effect on CRC is related to fatty acid degradation.

Previous studies have reported that m6a modification promotes tumor immune escape by affecting tumor microenvironment (TME). Due to the complexity of TME, a single biomarker is insufficient to describe the complex biological characteristics of tumor and its microenvironment. Therefore, it is more meaningful to explore a group of effective biomarkers reflecting different characteristics of cancer to evaluate the biological characteristics of solid tumors. Here, the immune gene CD34/CD276 with different m6A peak was obtained by m6A sequencing (MeRIP-seq) of colon cancer (CRC)clinical samples and combined with MsIgDB database, which was used to perform cluster analysis on TCGA-COAD level 3 data. The CD34/CD276 as a molecular marker for CRC prognosis was confirmed by survival analysis and immunohistochemical assay. Further bioinformatics analysis was carried out to analyze the molecular mechanism of CD34/CD276 affecting the TME through m6a-dependent down-regulation and ultimately promoting immune escape of CRC.