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长链非编码 RNA MALAT1 中的单倍型-GGGT 通过 MALAT1/miR-328/KATNB1 抑制脑转移肺癌和肺癌淋巴结。

Haplotype-GGGT in long non-coding RNA MALAT1 inhibits brain metastatic lung cancer and lymph nodes of lung cancer via the MALAT1/miR-328/KATNB1.

机构信息

Department of Medical Imaging, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.

Department of Magnetic Resonance Imaging, Dingbian County People’s Hospital, Dingbian, Yulin, Shaanxi 718600, China.

出版信息

Aging (Albany NY). 2023 Mar 2;15(6):1918-1930. doi: 10.18632/aging.204563.

Abstract

The up-regulation of katanin P80 has been reported to be correlated with a larger tumor size and lymph node metastasis in non-small-cell lung cancer (NSCLC) patients. And lncRNA MALAT1 was demonstrated to promote the proliferation of chronic myeloid leukemia cells via modulating miR-328. 135 lung cancer patients were divided into 6 groups according to their genotypes of MALAT1. The expression of KATNB1 was negatively correlated with the GGGT genotype of MALAT1. Decreased lymph node size and tumor size of brain metastatic lung were observed in patients with GGGT genotype of MALAT1. The luciferase activities of MALAT1 and KATNB1 were remarkably suppressed by miR-328 in A549 and H460. And the down-regulation of MALAT1 or up-regulation of miR-328 significantly repressed the KATNB1 expression in A549 and H460 cells. MALAT1 expression was reduced in patients carrying haplotype GGGT. A signaling pathway of MALAT1/miR-328/KATNB1 was established to explain the down-regulation of KATNB1 mRNA in patients carrying haplotype GGGT and reduced lymph node size in lung cancer and tumor size in brain metastatic lung cancer.

摘要

katanin P80 的上调已被报道与非小细胞肺癌(NSCLC)患者的更大肿瘤大小和淋巴结转移相关。并且长链非编码 RNA MALAT1 被证明通过调节 miR-328 促进慢性髓系白血病细胞的增殖。135 名肺癌患者根据 MALAT1 的基因型分为 6 组。KATNB1 的表达与 MALAT1 的 GGGT 基因型呈负相关。在 MALAT1 的 GGGT 基因型的患者中观察到脑转移肺癌的淋巴结大小和肿瘤大小减小。MALAT1 和 KATNB1 的荧光素酶活性在 A549 和 H460 中被 miR-328 显著抑制。并且 MALAT1 的下调或 miR-328 的上调显著抑制了 A549 和 H460 细胞中 KATNB1 的表达。携带杂合 GGGT 的患者中 MALAT1 表达降低。建立了 MALAT1/miR-328/KATNB1 的信号通路,以解释携带杂合 GGGT 的患者中 KATNB1 mRNA 的下调以及肺癌中淋巴结大小的减小和脑转移肺癌中的肿瘤大小的减小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ff/10085600/8df86ede20d4/aging-15-204563-g001.jpg

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