Hu Fang, Niu Yanjie, Mao Xiaowei, Cui Jiangtao, Wu Xiaoting, Simone Charles B, Kang Hye Seon, Qin Wenxin, Jiang Liyan
Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Transl Lung Cancer Res. 2021 Oct;10(10):3957-3972. doi: 10.21037/tlcr-21-829.
The biological role and clinical significance of transfer RNA-derived small RNAs (tsRNAs) remain largely unclear. The purpose of this study was to investigate the biological function, molecular mechanism, and clinical significance of tsRNA-5001a in lung adenocarcinoma.
The function of tsRNA-5001a on the growth of tumor cells was accessed by cell function experiments. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of tsRNA-5001a in paired samples of lung adenocarcinoma. Cell localization of tsRNA-5001a was performed by nuclear-cytoplasmic separation assay. Transcriptome sequencing was used to screen the molecules involved in the regulatory network of tsRNA-5001a. Independent samples -test was used to compare the two groups. Prism software (Prism 7.0) was used to analyze the statistical results. P<0.05 was considered statistically significant.
tsRNA-5001a was significantly upregulated in lung adenocarcinoma tissues. Upregulation of tsRNA-5001a was found to increase the risk of postoperative recurrences in patients with lung adenocarcinoma and was associated with poor prognosis. Function assay showed that overexpression tsRNA-5001a could significantly promote cell proliferation. In contrast, knockdown of tsRNA-5001a significantly inhibited the proliferation of lung adenocarcinoma cells. In addition, nucleoplasmic isolation assay indicated that tsRNA-5001a was located mainly in the cytoplasm. According to the results of RNA sequencing and The Cancer Genome Atlas database (TCGA database) analysis, growth arrest and DNA damage 45G () was screened and may be the target gene of tsRNA-5001a.
tsRNA-5001a promotes the proliferation of lung adenocarcinoma cells and increases the risk of postoperative recurrences in lung adenocarcinoma patients.
转运RNA衍生的小RNA（tsRNAs）的生物学作用和临床意义在很大程度上仍不清楚。本研究的目的是探讨tsRNA-5001a在肺腺癌中的生物学功能、分子机制及临床意义。
通过细胞功能实验评估tsRNA-5001a对肿瘤细胞生长的作用。采用实时定量聚合酶链反应（RT-qPCR）检测tsRNA-5001a在肺腺癌配对样本中的表达。通过核质分离实验进行tsRNA-5001a的细胞定位。利用转录组测序筛选参与tsRNA-5001a调控网络的分子。采用独立样本t检验比较两组数据。使用Prism软件（Prism 7.0）分析统计结果。P<0.05被认为具有统计学意义。
tsRNA-5001a在肺腺癌组织中显著上调。发现tsRNA-5001a的上调增加了肺腺癌患者术后复发的风险，并与预后不良相关。功能实验表明，过表达tsRNA-5001a可显著促进细胞增殖。相反，敲低tsRNA-5001a可显著抑制肺腺癌细胞的增殖。此外，核质分离实验表明tsRNA-5001a主要位于细胞质中。根据RNA测序结果和癌症基因组图谱数据库（TCGA数据库）分析，筛选出生长停滞和DNA损伤45G（GADD45G），其可能是tsRNA-5001a的靶基因。
tsRNA-5001a促进肺腺癌细胞增殖，并增加肺腺癌患者术后复发风险。
