Dataset Information

Chalcone suppresses tumor growth through NOX4-IRE1? sulfonation-RIDD-miR-23b axis.

ABSTRACT: Chalcone is a polyphenolic compound found abundantly in natural plant components. They have been acclaimed as potential antitumor compounds in multiple tumor cells. However, not much attention has been paid to elucidate its antitumor mechanism of action. Here, chalcone was demonstrated to trigger endoplasmic reticulum (ER) stress-induced apoptosis through sulfonation of IRE1? by ER-localized NADPH oxidase 4 (NOX4). IRE1?-sulfonation at a cysteine residue was shown to induce "regulated IRE1?-dependent decay" (RIDD) of mRNA rather than specific splicing of XBP1. The IRE1? sulfonation-induced RIDD degraded miR-23b, enhancing the expression of NOX4. The expression of NOX4 was also upregulated in breast, and prostate cancer tissue. In chalcone-administered mice in vivo, tumor growth was regressed by the consistent mechanisms "NOX4-IRE1? sulfonation-RIDD". Similarly, NOX4 activation and IRE1? sulfonation were also highly increased under severe ER stress conditions. Together, these findings suggest chalcone as a lead anticancer compound where it acts through NOX4-IRE1?-RIDD-miR-23b axis providing a promising vision of chalcone derivatives' anticancer mechanism.

SUBMITTER: Kim HK

PROVIDER: S-EPMC7806525 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Chalcone suppresses tumor growth through NOX4-IRE1α sulfonation-RIDD-miR-23b axis.

Kim Hyun-Kyoung HK Lee Hwa-Young HY Riaz Thoufiqul Alam TA Bhattarai Kashi Raj KR Chaudhary Manoj M Ahn Jin Hee JH Jeong Jieun J Kim Hyung-Ryung HR Chae Han-Jung HJ

Redox biology 20210106

Chalcone is a polyphenolic compound found abundantly in natural plant components. They have been acclaimed as potential antitumor compounds in multiple tumor cells. However, not much attention has been paid to elucidate its antitumor mechanism of action. Here, chalcone was demonstrated to trigger endoplasmic reticulum (ER) stress-induced apoptosis through sulfonation of IRE1α by ER-localized NADPH oxidase 4 (NOX4). IRE1α-sulfonation at a cysteine residue was shown to induce "regulated IRE1α-depe ...[more]

PMID: 33445069

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Project description:Ovarian cancer (OC), the third common gynecologic malignancy, contributes to the most cancer-caused mortality in women. However, 70% of patients with OC are diagnosed at an advanced stage, of which the 5-year survival is less than 30%. Long noncoding RNAs (long ncRNAs or lncRNA), a type of RNA with exceeding 200 nucleotides in length but no protein-coding capability, have been demonstrated to involve the pathogenesis of various cancers and show considerable potential in the diagnosis of OC. In this study, we found that the LINC00909 expression in tumor and serum specimens of OC patients was elevated, determined by real-time quantitative, and droplet digital PCR. In receiver operating characteristic (ROC) analysis, our results revealed that serum LINC00909 distinguished cancers from normal ovarian tissue with 87.8% of sensitivity and 69.6% of specificity (AUC, 81.2%) and distinguished serous ovarian cancer from normal ovarian tissue with 90.0% of sensitivity and 75.9% of specificity (AUC, 84.5%). Furthermore, we observed that the tumor and serum LINC00909 level was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and the Eastern Cooperative Oncology Group (ECOG) score (reflecting patients' performance status). Also, patients with low serum LINC00909 level showed a longer overall (hazard ratio, HR = 1.874, p = 0.0004) and progression-free (HR = 1.656, p = 0.0017) survival. Functional assays indicated that the elevation of LINC00909 expression contributes to cell proliferation, migration, and invasion capability of ovarian cancer cells. Besides, we demonstrated that LINC00909 functions as a competing endogenous RNA (ceRNA) of MRC2 mRNA by sponging miR-23-3p, and thereby promotes epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells. Therefore, we highlight that the LINC00909/miR-23b-3p/MRC2 axis is implicated in the pathogenesis of ovarian cancer, and serum LINC00909 may be a promising biomarker for the diagnosis of OC.

Dataset Information

Chalcone suppresses tumor growth through NOX4-IRE1? sulfonation-RIDD-miR-23b axis.

Publications

Chalcone suppresses tumor growth through NOX4-IRE1α sulfonation-RIDD-miR-23b axis.

Similar Datasets

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