Jeong Hyorim, Choi Kangchan, Hwang Dasom, Park Sunyoung, Park Yong Serk, Lee Hyeyoung
College of Engineering and Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
School of Medicine, Trinity Medical Sciences University, Ribishi VC0272, Saint Vincent and the Grenadines.
Curr Issues Mol Biol. 2024 Nov 8;46(11):12704-12717. doi: 10.3390/cimb46110754.
HPV/pap tests are widely used for cervical cancer screening, playing a crucial role in early diagnosis and guiding future treatment options. However, approximately 50% of cervical cancer patients are diagnosed at an advanced stage, which is associated with higher recurrence rates and poorer survival outcomes than early-stage diagnoses. This underscores the need for effective treatments for advanced-stage cervical cancer. Among the various oncogenes implicated in cancer, PIK3CA expression is known to cause cervical cancer, suggesting that inhibiting PIK3CA may impede cervical cancer progression. In this study, we transfected PIK3CA-overexpressing tumor cells (SiHa, C33A, and HeLa) with miR-29a, a microRNA extensively studied as a therapeutic candidate for oncogene suppression in various tumor types. We conducted RT-qPCR and Western blot analyses to assess changes in PIK3CA expression at the RNA and protein levels. Wound healing and cell migration assays were used to evaluate the effects of miR-29a on cell division and migration in HeLa cells. We confirmed a reduction in PIK3CA expression at both RNA and protein levels following miR-29a transfection. After transfecting miR-29a into HeLa cells, we observed a reduction in cell division and migration, as demonstrated by wound healing and cell migration assays. Additionally, we found that miR-29a binds to the 3'-UTR region of PIK3CA, leading to a reduction in its gene expression. Furthermore, we correlated the concentration of miR-29a in clinical histologic biopsy samples from cervical cancer patients with disease progression. These findings indicate that miR-29a can slow the progression of cervical cancer by targeting PIK3CA and potentially aid in its treatment. miR-29a shows promise as a therapeutic agent for inhibiting oncogene expression and controlling cervical cancer progression, especially in advanced-stage cases.
人乳头瘤病毒/巴氏涂片检查被广泛用于宫颈癌筛查，在早期诊断和指导未来治疗方案方面发挥着关键作用。然而，约50%的宫颈癌患者在晚期才被诊断出来，与早期诊断相比，这与更高的复发率和更差的生存结果相关。这凸显了对晚期宫颈癌进行有效治疗的必要性。在与癌症相关的各种致癌基因中，已知PIK3CA表达会导致宫颈癌，这表明抑制PIK3CA可能会阻碍宫颈癌的进展。在本研究中，我们用miR-29a转染了过表达PIK3CA的肿瘤细胞（SiHa、C33A和HeLa），miR-29a是一种作为各种肿瘤类型中致癌基因抑制治疗候选物而被广泛研究的微小RNA。我们进行了逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析，以评估PIK3CA在RNA和蛋白质水平上的表达变化。伤口愈合和细胞迁移试验用于评估miR-29a对HeLa细胞分裂和迁移的影响。我们证实了miR-29a转染后PIK3CA在RNA和蛋白质水平上的表达均降低。将miR-29a转染到HeLa细胞后，如伤口愈合和细胞迁移试验所示，我们观察到细胞分裂和迁移减少。此外，我们发现miR-29a与PIK3CA的3'-非翻译区（3'-UTR）区域结合，导致其基因表达降低。此外，我们将宫颈癌患者临床组织活检样本中miR-29a的浓度与疾病进展相关联。这些发现表明，miR-29a可以通过靶向PIK3CA来减缓宫颈癌的进展，并可能有助于其治疗。miR-29a有望作为一种治疗剂，用于抑制致癌基因表达和控制宫颈癌进展，尤其是在晚期病例中。
