T-cell lymphoblastic lymphoma (T-LBL) is a class of highly aggressive hematologic neoplasms originating from progenitor T-lymphocytes. MicroRNA (miRNA) is an endogenous RNA molecule with 22 nucleotides in length. Accumulated evidence suggests that miRNA functions as a key regulator in human cancer. Herein, by in silico analysis, we found that miR-211 was a decreased miRNA in T-LBL in high-throughput sequencing data, which was subsequently verified in our cohort. Low miR-211 was closely correlated with bulky disease, high ann arbor stage, relapse and poor prognosis. miR-211 was regulated by N6-methyladenosine (m⁶A) modification, specifically, m6A methyltransferase METTL14 methylated primary miR-211 (pri-miR-211), expediting pri-miR-211 processing via recruiting DGCR8. Functionally, miR-211 overexpression significantly reduced T-LBL cell viability, DNA synthesis rate and spheroid formation ability, whereas silencing of miR-211 had the opposite effects. In addition, we established the xenograft tumor model and found that miR-211 remarkably inhibited tumor growth in vivo. Further, TCF12 was the direct target of miR-211, miR-211 bound to TCF12 mRNA 3`-untranslated region (UTR) and increased its decay, overexpression of TCF12 could effectively rescue the weakened malignant behavior of T-LBL cells caused by miR-211 overexpression. Collectively, our data clearly demonstrate that miR-211 is a novel tumor suppressor in T-LBL, targeting of miR-211/TCF12 axis may be a potential treatment for T-LBL patients.

T 细胞淋巴母细胞淋巴瘤 (T-LBL) 是一类起源于祖 T 淋巴细胞的高度侵袭性血液肿瘤。MicroRNA (miRNA) 是一种内源性 RNA 分子，长度为 22 个核苷酸。积累的证据表明，miRNA 在人类癌症中起关键调节作用。在此，通过计算机分析，我们发现 miR-211 在高通量测序数据中是 T-LBL 中减少的 miRNA，随后在我们的队列中得到验证。低miR-211与大块病、高Annarbor分期、复发和不良预后密切相关。miR-211 受 N6-甲基腺苷 (m ⁶ A) 修饰的调控，特别是 m6A 甲基转移酶 METTL14 甲基化初级 miR-211 (pri-miR-211)，通过招聘 DGCR8。在功能上，miR-211 过表达显着降低了 T-LBL 细胞活力、DNA 合成率和球体形成能力，而 miR-211 的沉默具有相反的效果。此外，我们建立了异种移植肿瘤模型，发现miR-211在体内显着抑制肿瘤生长。此外，TCF12是miR-211的直接靶点，miR-211与TCF12 mRNA 3`-非翻译区（UTR）结合并增加其衰减，TCF12的过表达可以有效挽救miR引起的T-LBL细胞恶性行为减弱-211 过度表达。总的来说，我们的数据清楚地表明 miR-211 是 T-LBL 中的一种新型肿瘤抑制因子，靶向 miR-211/TCF12 轴可能是 T-LBL 患者的潜在治疗方法。