Department of Gynecology, Clinical Laboratory, Linyi Cancer Hospital, Linyi, Shandong, China.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5611-5620. doi: 10.26355/eurrev_201907_18295.
It is well verified that lncRNA are emerging as imperative regulators in various tumors. LncRNA CALML3-AS1 (CALML3-AS1), a freshly discovered lncRNA, has been confirmed as a tumor promoter in bladder cancer. This present study aimed to explore the biological functions and molecular mechanisms of CALML3-AS1 in cervical cancer (CC).
We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) datasets to determine dysregulated lncRNAs in CC. Real Time-Polymerase Chain Reaction (RT-PCR) was applied for the assays of CALML3-AS1 amplification in CC samples and cell lines. Kaplan-Meier analysis and multivariate assays were carried out for determination of the prognostic values. The functions of CALML3-AS1 on cell proliferation, invasion, migration, and apoptosis were determined by a series of cells experiments by knocking down CALML3-AS1. MRNA and protein expressions of signaling pathways were examined using Western blot.
We found that CALML3-AS1 was upregulated in CC tissues and this upregulation was associated with FIGO stage, histological grade, and reduced overall survival. Multivariate assays indicated that high CALML3-AS1 expression was an independent prognostic parameter indicating poorer clinical outcome for CC patients. Functional assays suggested that knockdown of CALML3-AS1 suppressed the proliferation, migration, and invasion of CC cells, and induced apoptosis. Mechanistic investigations revealed that inhibiting the expression of CALML3-AS1 decreased the levels of β-catenin, cyclin D1, and c-myc via Western blot.
Our study revealed that CALML3-AS1 could be an oncogenic lncRNA promoting the growth and metastasis of CC by modulating Wnt/β-catenin pathway, suggesting that CALML3-AS1 may be an important contributor to CC progression.
lncRNA 作为各种肿瘤中重要的调节因子已经得到了很好的验证。LncRNA CALML3-AS1（CALML3-AS1）是一种新发现的 lncRNA，已被证实为膀胱癌的肿瘤促进因子。本研究旨在探讨 CALML3-AS1 在宫颈癌（CC）中的生物学功能和分子机制。
我们分析了来自癌症基因组图谱（TCGA）数据集的 RNA 测序数据，以确定 CC 中失调的 lncRNA。实时聚合酶链反应（RT-PCR）用于 CC 样本和细胞系中 CALML3-AS1 扩增的检测。采用 Kaplan-Meier 分析和多变量分析确定预后价值。通过敲低 CALML3-AS1，一系列细胞实验确定 CALML3-AS1 对细胞增殖、侵袭、迁移和凋亡的功能。使用 Western blot 检测信号通路的 mRNAs 和蛋白表达。
我们发现 CALML3-AS1 在 CC 组织中上调，这种上调与 FIGO 分期、组织学分级和总生存率降低有关。多变量分析表明，CALML3-AS1 高表达是 CC 患者预后不良的独立预后参数。功能分析表明，敲低 CALML3-AS1 抑制了 CC 细胞的增殖、迁移和侵袭，并诱导了细胞凋亡。机制研究表明，通过 Western blot，抑制 CALML3-AS1 的表达降低了 β-catenin、cyclin D1 和 c-myc 的水平。
我们的研究表明，CALML3-AS1 可能通过调节 Wnt/β-catenin 通路促进 CC 的生长和转移，从而成为一种致癌 lncRNA，表明 CALML3-AS1 可能是 CC 进展的重要因素。
