Zhang Ying, Sun Yi, Ding Lin, Shi Wenjing, Ding Keshuo, Zhu Yong
Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Department of Oncology of the First Affiliated Hospital, Division of Life Science and Medicine, The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, China.
Front Oncol. 2021 Apr 28;11:643394. doi: 10.3389/fonc.2021.643394. eCollection 2021.
Breast cancer remains the leading cause of female cancer-related mortalities worldwide. Long non-coding RNAs (LncRNAs) have been increasingly reported to play pivotal roles in tumorigenesis and cancer progression. Herein, we focused on LINC00467, which has never been studied in breast cancer. Silence of LINC00467 suppressed proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) of breast cancer cells , whereas forced expression of LINC00467 exhibited the opposite effects. Furthermore, we demonstrated overexpression of LINC00467 promoted tumor growth, while knockdown of LINC00467 inhibited pulmonary metastasis Mechanistically, LINC00467 down-regulated miR-138-5p by acting as a miRNA "sponge". Besides, LINC00467 also up-regulated the protein level of lin-28 homolog B (LIN28B) a direct interaction. A higher expression level of LINC00467 was observed in breast cancer tissues as compared to the adjacent normal counterparts and elevated LINC00467 predicted poor overall survival. Our findings suggest LINC00467 promotes progression of breast cancer through interacting with miR-138-5p and LIN28B directly. LINC00467 may serve as a potential candidate for the diagnosis and treatment of breast cancer.
乳腺癌仍然是全球女性癌症相关死亡的主要原因。越来越多的研究报道长链非编码RNA（LncRNAs）在肿瘤发生和癌症进展中起关键作用。在此，我们聚焦于LINC00467，其在乳腺癌中从未被研究过。沉默LINC00467可抑制乳腺癌细胞的增殖、迁移、侵袭和上皮-间质转化（EMT），而强制表达LINC00467则表现出相反的效果。此外，我们证明LINC00467的过表达促进肿瘤生长，而敲低LINC00467则抑制肺转移。机制上，LINC00467通过充当miRNA“海绵”下调miR-138-5p。此外，LINC00467还通过直接相互作用上调lin-28同源物B（LIN28B）的蛋白水平。与相邻正常组织相比，在乳腺癌组织中观察到LINC00467的表达水平更高，且LINC00467升高预示着总体生存率较差。我们的研究结果表明，LINC00467通过直接与miR-138-5p和LIN28B相互作用促进乳腺癌进展。LINC00467可能是乳腺癌诊断和治疗的潜在候选者。
