LINC00461 Regulates the Recurrence of Large B Cell Lymphoma through the miR-411-5p/BNIP3 Pathway

Shu-Wen Sun; Yan Chen; Hui-Juan Liao; Wei Zhang; Wen-Ming Xu; Guo-Qian He

doi:10.1155/2022/9100056

LINC00461 Regulates the Recurrence of Large B Cell Lymphoma through the miR-411-5p/BNIP3 Pathway

Evid Based Complement Alternat Med. 2022 Jun 24:2022:9100056. doi: 10.1155/2022/9100056. eCollection 2022.

Authors

Shu-Wen Sun^{1

2}, Yan Chen^{1

3}, Hui-Juan Liao^{1

3}, Wei Zhang⁴, Wen-Ming Xu^{1

3}, Guo-Qian He^{1

2}

Affiliations

¹ Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
² Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
³ Joint Laboratory of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
⁴ Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, Chengdu, Sichuan 610041, China.

Abstract

Objective: To analyze the mechanism of LINC00461 regulating the recurrence of diffuse large B cell lymphoma (DLBCL) through microRNA (miR)-411-5p/BCL2 interacting protein 3 (BNIP3) pathway.

Methods: DLBCL samples in TCGA and GSE12453 were used for differential analysis to find long noncoding RNA (lncRNA) related to DLBCL recurrence. The 4 DLBCL data with the highest and lowest expression levels of LINC00461 in the TCGA database were selected for GSEA enrichment analysis. The targeting relationships of miR-411-5p with LINC00461 and BNIP3 were verified by the dual luciferase report. Blood samples from DLBCL patients were used to analyze the correlation between miR-411-5p and LINC00461 or BNIP3. LINC00461, miR-411-5p, or BNIP3 was overexpressed or silenced by transfection, and a tumor-bearing nude mice model was constructed to detect their effects on proliferation and apoptosis.

Results: The level of LINC00461 in DLBCL was significantly higher than that in normal cases, and the level in recurrence DLBCL was significantly higher than that in nonrecurrence. The enrichment analysis results showed that the function of LINC00461 was closely related to apoptosis. The results shown that miR-411-5p bound to LINC00461 and BNIP3 and was negatively correlated with LINC00461 and BNIP3 mRNA in blood of DLBCL patients. Suppressing the level of LINC00461 inhibited cell proliferation and induced apoptosis. The inhibition of LINC00461 or overexpression of miR-411-5p reduced the expression of BNIP3 protein, thereby inducing apoptosis at the in vivo and in vitro levels.

Conclusion: LINC00461 may induce miR-411-5p to "sponge," thereby increasing the expression of BNIP3 protein, and exerting the function of inhibiting apoptosis and promoting DLBCL recurrence.