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长非编码 RNA(lncRNA)金属硫蛋白 1J,假基因(MT1JP)在三阴性乳腺癌中下调,并上调 microRNA-138(miR-138)下调缺氧诱导因子-1α(HIF-1α)。

Long noncoding RNA (lncRNA) metallothionein 1 J, pseudogene (MT1JP) is downregulated in triple-negative breast cancer and upregulates microRNA-138 (miR-138) to downregulate hypoxia-inducible factor-1α (HIF-1α).

机构信息

Department of Breast, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

出版信息

Bioengineered. 2022 May;13(5):13718-13727. doi: 10.1080/21655979.2022.2077906.

Abstract

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study explored the molecular mechanism and influences of metallothionein 1 J, pseudogene (MT1JP), microRNA-138 (miR-138), and hypoxia-inducible factor-1α (HIF-1α) on TNBC cell proliferation and migration. We confirmed TNBC cases by immunohistochemistry (IHC) staining. The expression of MT1JP in two types of tissue collected from 78 TNBC patients was detected by performing real-time quantitative fluorescence PCR (RT-qPCR). To further evaluate the relationship among MT1JP, miR-138 and HIF-1α, expression vectors of MT1JP and HIF-1α, as well as miR-138 mimic and inhibitor, were delivered into BT-549 cells. We observed that MT1JP was downregulated in TNBC. MT1JP was positively correlated with miR-138 but negatively correlated with HIF-1α in TNBC tissues. In TNBC cells, upregulation of miR-138 and downregulation of HIF-1α were observed after overexpression of MT1JP. In addition, overexpression of miR-138 resulted in downregulation of HIF-1α but did not affect the expression of MT1JP. Decreased proliferation rate of TNBC cells was observed after overexpression of MT1JP and miR-138. HIF-1α increased cell proliferation and migration. HIF-1α also suppressed the role of MT1JP and miR-138 in TNBC cell proliferation and migration. In conclusion, our findings demonstrated that MT1JP inhibited TNBC by regulating the miR-138/HIF-1α axis, indicating that MT1JP might serve as a biomarker or target for TNBC treatment.

摘要

三阴性乳腺癌(TNBC)是一种高度侵袭性的乳腺癌亚型。本研究探讨了金属硫蛋白 1J、假基因(MT1JP)、微小 RNA-138(miR-138)和缺氧诱导因子-1α(HIF-1α)对 TNBC 细胞增殖和迁移的分子机制和影响。我们通过免疫组织化学(IHC)染色证实了 TNBC 病例。通过实时荧光定量 PCR(RT-qPCR)检测 78 例 TNBC 患者两种组织中 MT1JP 的表达。为了进一步评估 MT1JP、miR-138 和 HIF-1α 之间的关系,我们将 MT1JP 和 HIF-1α 的表达载体以及 miR-138 模拟物和抑制剂转染到 BT-549 细胞中。我们发现 MT1JP 在 TNBC 中下调。在 TNBC 组织中,MT1JP 与 miR-138 呈正相关,与 HIF-1α 呈负相关。在 TNBC 细胞中,过表达 MT1JP 后观察到 miR-138 上调和 HIF-1α 下调。此外,过表达 miR-138 导致 HIF-1α 下调,但不影响 MT1JP 的表达。过表达 MT1JP 和 miR-138 后,TNBC 细胞增殖率降低。HIF-1α 增加细胞增殖和迁移。HIF-1α 还抑制了 MT1JP 和 miR-138 在 TNBC 细胞增殖和迁移中的作用。综上所述,我们的研究结果表明,MT1JP 通过调节 miR-138/HIF-1α 轴抑制 TNBC,表明 MT1JP 可能作为 TNBC 治疗的标志物或靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05fc/9276039/62b323854701/KBIE_A_2077906_UF0001_OC.jpg

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