c‐Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T‐cell lymphoma

Abstract

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor outcomes. The treatment of NKTCL requires intensive chemotherapy.Long noncoding RNAs (lncRNAs) have been implicated in many cancers, including NKTCL. The elucidation of the multidrug resistance (MDR) may greatly contribute to explore novel therapeutic strategies. Herein, we explored the roles and potential regulatory mechanism of lncRNAs small nucleolar RNA host gene 12 (SNHG12) in MDR of NKTCL. We found that SNHG12 was upregulated in NKTCL tissue sections, and its high expression was positively correlated with clinical grade of malignancy of NKTCL. c-Myc and SNHG12 expression was upregulated in NKTCL cell lines. c-Myc-and SNHG12 overexpression promoted proliferation and inhibited sensitivity to cisplatin (CDDP) in NK/T-cell lymphoma cell line YTS cells, and c-Myc and SNHG12-downregulation inhibited proliferation and enhanced sensitivity to CDDP in SNK-6 cells. Moreover, c-Myc-and SNHG12 overexpression increased Ki67 and P-gp expression in YTS cells, whereas c-Myc and SNHG12downregulation reduced the Ki67 and P-gp expression in SNK-6 cells. Correlational analyses revealed that c-Myc expression was positively correlated with SNHG12 expression in NKTCL tissues. Mechanism research showed that SNHG12 was a direct transcriptional target of c-Myc and c-Myc promoted SNHG12 expression in NKTCL cell lines. Further research showed that SNHG12 overexpression reversed the effects of c-Myc downregulation on proliferation and sensitivity to CDDP in NKTCL cell lines. Taken together, our findings first report that c-Myc mediated upregulation of SNHG12 promotes proliferation and inhibits drug sensitivity in NKTCL, which provides new insights into the therapeutic target for NKTCL. K E Y W O R D S c-Myc, drug sensitivity, natural killer/T-cell lymphoma, proliferation, SNHG12

Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC

“…4B). Interestingly, multiple small nucleolar RNA host genes were recently frequently reported in cancers (Damas et al, 2016;Dong et al, 2018;Guo et al, 2018;Jiang et al, 2018a;Shan et al, 2018;Sun et al, 2017;Xu et al, 2018;Zhu et al, 2019). In ESCC, we found that knockdown of SNHG10, an uncharacterized lncRNA, reduced proliferation, migration, and clonogenicity in KYSE150 and TE3 cells (Fig.…”

Long Noncoding RNA SNHG12 is a Potential Diagnostic and Prognostic Biomarker in Various Tumors

“…Due to the heterogeneity of tumors and the complexity of the tumor microenvironment, these molecules can play a carcinogenic or tumor suppressive role in the same tumor. There is evidence that lncRNAs can act as molecular scaffolds, sponges or coactivators in tumor scaffolds by interacting with DNA, RNA or proteins [5,31,32] . At present, increasing evidence has shown that the abnormally high expression of SNHG12 plays a carcinogenic role in various malignant tumors [10][11][12][13][14][15][16][17][18][19][26][27][28][29] .…”

“…Further research has shown that overexpression of SNHG12 is associated with rapid cancer proliferation, strong invasion and migration, and high rates of metastasis, recurrence, and chemical resistance [30][31][32] (Table 7). Moreover, in lung cancer, this molecule can inhibit metastasis and epithelial-mesenchymal transition when inhibited [12] .…”

“…Moreover, in lung cancer, this molecule can inhibit metastasis and epithelial-mesenchymal transition when inhibited [12] . Furthermore, increased SNHG12 not only regulates malignant behavior by activating oncogenes (AMOT, HuR slug/ZEB2) [12,33,34] , signaling pathways (MAPK/Slug, wnt/β-catenin, and Notch signaling pathway) [10,11,29,30,35] and the microRNA-gene axis (miR-125b/STAT3 and miR-101-3p/FOXP1) [27,31,36] but also enhances chemoresistance of tumor cells [31,32,37] . SNHG12 is negative regulation miR-195-5p, miR-320, miR-129, miR-193a-3p, microRNA-199a/b-5p and miR-424-5 [11,14,15,17,26] .…”

Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application

“…Overexpression of lncRNA GAS5 decreased miR-544 expression and increased RUNX3 expression, IFN-γ secretion and NK cell cytotoxicity [53]. It has been reported that lncRNA SNHG12 is a direct transcriptional target of c-Myc and that c-Myc-mediated upregulation of lncRNA SNHG12 expression promotes proliferation and inhibits sensitivity to cisplatin (CDDP) in natural killer/T-cell lymphoma [54]. In parallel, Ma and colleagues demonstrated that circRNA of AR-suppressed PABPC1 91 bp enhanced the cytotoxicity of natural killer cells against hepatocellular carcinoma.…”