Hsieh Jia-Juan, Hou Ming-Mo, Chang John Wen-Cheng, Shen Yung-Chi, Cheng Hsin-Yi, Hsu Todd
Department of Bioscience and Biotechnology and Center of Excellence for The Oceans, National Taiwan Ocean University, Keelung 20224, Taiwan, R.O.C.
Division of Hematology-Oncology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan, R.O.C.
Oncol Lett. 2019 Sep;18(3):2598-2604. doi: 10.3892/ol.2019.10547. Epub 2019 Jun 28.
Ras-related protein Rab-38 (RAB38) is a member of the Ras small G protein family that regulates intracellular vesicular trafficking. Although the expression of is reportedly deregulated in several types of cancer, its role in tumor biology remains to be elucidated. In the present study, the expression of was analyzed in tumor specimens from patients with non-small cell lung cancer (NSCLC) with tumor recurrence within 4 years (Group R), and those remaining disease-free following initial surgery (Group NR), by reverse transcription-semi-quantitative PCR and subsequent semi-quantification using ImageJ v4.0 software. The results revealed that the expression of in Group R and NR specimens was positively associated with tumor recurrence; a high expression level was also associated with poor survival rate in these patients. Using NSCLC cell lines, it was demonstrated that tumor cells with mutations in the active epidermal growth factor receptor (EGFR) gene expressed higher levels of RAB38 compared with those with the wild-type gene by reverse transcription-PCR and western blot analysis. Furthermore, following specific RAB38 gene knockdown by short hairpin RNA transfection, mutants exhibited markedly reduced invasiveness when compared with cells transfected with empty vector controls by Matrigel Transwell assays. These results suggest that is an important prognostic factor in NSCLC, and may serve a critical role in NSCLC-associated tumor metastasis.
Ras相关蛋白Rab-38(RAB38)是Ras小G蛋白家族的成员,可调节细胞内囊泡运输。尽管据报道其在几种类型的癌症中表达失调,但其在肿瘤生物学中的作用仍有待阐明。在本研究中,通过逆转录-半定量PCR以及随后使用ImageJ v4.0软件进行半定量分析,对4年内出现肿瘤复发的非小细胞肺癌(NSCLC)患者(R组)和初次手术后无疾病复发的患者(NR组)的肿瘤标本中RAB38的表达进行了分析。结果显示,R组和NR组标本中RAB38的表达与肿瘤复发呈正相关;高表达水平还与这些患者的低生存率相关。利用NSCLC细胞系,通过逆转录PCR和蛋白质印迹分析表明,与野生型基因的细胞相比,活性表皮生长因子受体(EGFR)基因突变的肿瘤细胞表达更高水平的RAB38。此外,通过短发夹RNA转染特异性敲低RAB38基因后,与用空载体对照转染的细胞相比,在基质胶Transwell试验中,RAB38突变体的侵袭性明显降低。这些结果表明,RAB38是NSCLC的一个重要预后因素,并且可能在NSCLC相关的肿瘤转移中起关键作用。