Liu Weipeng, Huang Fengdan, Yao Yueting, Liang Yan, Yan Zhiling, Guo Lili, Zhang Xinwen, Shi Li, Yao Yufeng
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China.
Graduate School of Yunnan University, Yunnan University, Kunming, Yunnan, China.
Front Oncol. 2024 Sep 13;14:1440906. doi: 10.3389/fonc.2024.1440906. eCollection 2024.
Cervical cancer stands as one of the leading causes of cancer-related mortality in women worldwide, yet the precise functions of host genes implicated in its pathogenesis remain elusive. Genome-wide association studies (GWAS) have revealed a significant association between the CLPTM1L locus and cervical cancer risk in European women, and aberrant expression of CLPTM1L has been noted in various malignant tumors. However, the role of CLPTM1L in cervical cancer remains largely unexplored.
The expression of CLPTM1L in cervical cancer cells and tissues was detected by RT-qPCR. Furthermore, the potential biological functions of CLPTM1L in the context of cervical cancer were explored via RNA sequencing. Cell proliferation rates and the responsiveness of cervical cancer cells to cisplatin were evaluated using the CCK-8 assay, while cell apoptosis was quantified through the utilization of flow cytometry. Nude mouse xenograft models were utilized to explore the impact of CLPTM1L on tumor formation .
Our findings demonstrated a significant increase in CLPTM1L mRNA expression levels in HeLa and C33A cells, as well as in cervical carcinoma tissues, compared to ECT1/E6E7 cells and adjacent normal tissues. Genes related to CLPTM1L were found to be enriched in the Hedgehog signaling pathway. and studies showed that reducing CLPTM1L expression markedly inhibited cell proliferation via downstream candidate genes BOC and LRP2. Furthermore, the downregulation of CLPTM1L was found to enhance cisplatin-induced cell apoptosis and increase the susceptibility of cervical cancer cells to cisplatin through DAP1.
CLPTM1L could impact cervical cancer cell proliferation and cisplatin-induced cell apoptosis, as well as cisplatin susceptibility in cervical cancer cells. This investigation has bestowed upon us novel insights into the pathogenesis of cervical cancer, underscoring the potential of CLPTM1L as a promising target for chemotherapeutic sensitization in the management of this malignancy.
宫颈癌是全球女性癌症相关死亡的主要原因之一，但其发病机制中宿主基因的确切功能仍不清楚。全基因组关联研究（GWAS）已揭示CLPTM1L基因座与欧洲女性宫颈癌风险之间存在显著关联，并且在各种恶性肿瘤中已注意到CLPTM1L的异常表达。然而，CLPTM1L在宫颈癌中的作用在很大程度上仍未得到探索。
通过RT-qPCR检测CLPTM1L在宫颈癌细胞和组织中的表达。此外，通过RNA测序探索CLPTM1L在宫颈癌背景下的潜在生物学功能。使用CCK-8测定法评估细胞增殖率和宫颈癌细胞对顺铂的反应性，同时通过流式细胞术对细胞凋亡进行定量。利用裸鼠异种移植模型探索CLPTM1L对肿瘤形成的影响。
我们的研究结果表明，与ECT1/E6E7细胞和相邻正常组织相比，HeLa和C33A细胞以及宫颈癌组织中CLPTM1L mRNA表达水平显著增加。发现与CLPTM1L相关的基因在Hedgehog信号通路中富集。 和 研究表明，降低CLPTM1L表达通过下游候选基因BOC和LRP2显著抑制细胞增殖。此外，发现CLPTM1L的下调通过DAP1增强顺铂诱导的细胞凋亡并增加宫颈癌细胞对顺铂的敏感性。
CLPTM1L可能影响宫颈癌细胞增殖、顺铂诱导的细胞凋亡以及宫颈癌细胞对顺铂的敏感性。这项研究为我们提供了关于宫颈癌发病机制的新见解，强调了CLPTM1L作为这种恶性肿瘤化疗增敏的有希望靶点的潜力。
