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HOTAIR诱导胃癌细胞系中miR-200家族成员的下调。

HOTAIR Induces the Downregulation of miR-200 Family Members in Gastric Cancer Cell Lines.

作者信息

Bossaghzadeh Fatemeh, Hajjari Mohammadreza, Sheikhi Abdolkarim, Salahshourifar Iman, Irani Shiva

机构信息

Department of Biology, Science and research Branch, Islamic Azad University, Tehran, Iran.

Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

出版信息

Iran Biomed J. 2022 Jan 1;26(1):77-84. doi: 10.52547/ibj.26.1.77.

Abstract

BACKGROUND

Gastric cancer (GC) is the fourth most common human malignancy and the second reason for cancer morbidity worldwide. Long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) has recently emerged as a promoter of metastasis in various cancer types, including GC, through the epithelial‑mesenchymal transition (EMT) process. However, the exact mechanism of HOTAIR in promoting EMT is unknown. Aberrant expression of the miR-200 family has been linked to the occurrence and development of various types of malignant tumors. This study investigates the correlation between the HOTAIR and miR-200 family gene expression patterns in GC cell lines. We investigated the miR-200 and HOTAIR due to their common molecular features in the EMT process.

METHODS

AGS and MKN45 cell lines were transfected with si-HOTAIR, along with a negative control. The effect of HOTAIR knockdown was also analyzed on cell viability and also on the expression of miR-200 family members, including miR-200a, -200b, and -200c, in cell lines using qRT-PCR. Statistical analysis was performed to find the potential correlation between the expression level of HOTAIR and miRs.

RESULTS

Our results showed significant increased miR-200 family expression level in transfected AGS and MKN45 GC cells (fold changes > 2; p < 0.001). Moreover, a negative correlation was observed between HOTAIR and miR-200 expression levels in GC cell lines (p < 0.05).

CONCLUSION

Our findings showed a significant association between miR-200 family and HOTAIR expression levels in GC cell lines. Taken together, the HOTAIR-miR-200 axis seems to play a vital role in human GC, suggesting a potential therapeutic target in future GC treatment.

摘要

背景

胃癌(GC)是全球第四大常见人类恶性肿瘤,也是癌症发病的第二大原因。长链非编码RNA(LncRNA)HOX转录反义RNA(HOTAIR)最近已成为包括GC在内的多种癌症类型中转移的促进因子,其通过上皮-间质转化(EMT)过程发挥作用。然而,HOTAIR促进EMT的确切机制尚不清楚。miR-200家族的异常表达与各种类型恶性肿瘤的发生和发展有关。本研究调查了GC细胞系中HOTAIR与miR-200家族基因表达模式之间的相关性。由于它们在EMT过程中具有共同的分子特征,我们对miR-200和HOTAIR进行了研究。

方法

将小干扰RNA(si-HOTAIR)与阴性对照一起转染AGS和MKN45细胞系。还使用qRT-PCR分析了HOTAIR敲低对细胞活力以及细胞系中miR-200家族成员(包括miR-200a、-200b和-200c)表达的影响。进行统计分析以发现HOTAIR表达水平与miR之间的潜在相关性。

结果

我们的结果显示,转染后的AGS和MKN45 GC细胞中miR-200家族表达水平显著升高(倍数变化>2;p<0.001)。此外,在GC细胞系中观察到HOTAIR与miR-200表达水平呈负相关(p<0.05)。

结论

我们的研究结果显示GC细胞系中miR-200家族与HOTAIR表达水平之间存在显著关联。综上所述,HOTAIR-miR-200轴似乎在人类GC中起着至关重要的作用,这表明其可能是未来GC治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18a8/8784900/5d449330abe6/ibj-26-77-g001.jpg

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