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Pseudogene CSPG4P12 affects the biological behavior of non‑small cell lung cancer by Bcl‑2/Bax mitochondrial
Wenqian Hu1,2, Hongjiao Wu1, Ang Li1
1School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China.
Abstract:
Increasing evidence has shown that chondroitin sulfate proteoglycan 4 (CSPG4) serve a critical role in tumor progression. However, the roles of chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) remain to be elucidated. The present study aimed to investigate the potential effects of CSPG4P12 on the physiological behaviors of non-small cell lung cancer (NSCLC) and its underlying biological mechanism. The expression levels of CSPG4P12 in NSCLC tissues and adjacent normal tissues were analyzed using the gene expression profiling interactive analysis 2 database and reverse transcription-quantitative PCR. Cell Counting Kit-8 and colony formation assays were performed to measure cell proliferation. In addition, Transwell and wound healing assays were performed to assess cell invasion and migration. Cell adhesion was measured by cell-extracellular matrix adhesion assay. Hoechst 33342 staining assay was performed to detect nucleoli of apoptotic cells, and transmission electron microscopy (TEM) was utilized for apoptosis detection. Immunofluorescence and western blot assays were performed to measure the expression levels of apoptosis-related proteins. The present results revealed that the expression levels of CSPG4P12 in NSCLC tissues were significantly lower compared with those in adjacent normal tissues. Overexpression of CSPG4P12 inhibited cell proliferation, invasion, migration and adhesion whilst promoting apoptosis. There were missing mitochondrial cristae and mitochondrial vacuoles in the CSPG4P12-overexpressed cells when observed under TEM. Overexpression of CSPG4P12 also increased the expression of Bax and p53, whereas it inhibited the expression of Bcl2. In conclusion, CSPG4P12 could inhibit NSCLC development and tumorigenesis by activating the p53/Bcl2/Bax mitochondrial apoptotic pathway.
Insights
Chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) is downregulated in non-small cell lung cancer (NSCLC). Overexpressing CSPG4P12 inhibits NSCLC progression by promoting apoptosis via the p53/Bcl2/Bax pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chondroitin sulfate proteoglycan 4 (CSPG4) is implicated in tumor progression.
- The specific role of chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) in non-small cell lung cancer (NSCLC) is not well understood.
Purpose of the Study:
- To investigate the functional role of CSPG4P12 in NSCLC.
- To elucidate the underlying molecular mechanisms by which CSPG4P12 affects NSCLC physiology.
Main Methods:
- Analysis of CSPG4P12 expression in NSCLC tissues versus normal tissues using bioinformatics and RT-qPCR.
- Assessment of cell proliferation, invasion, migration, and adhesion using various in vitro assays.
- Detection of apoptosis and related protein expression (Bax, p53, Bcl2) via microscopy and Western blot.
Main Results:
- CSPG4P12 expression was significantly lower in NSCLC tissues compared to adjacent normal tissues.
- Overexpression of CSPG4P12 suppressed NSCLC cell proliferation, invasion, migration, and adhesion.
- CSPG4P12 overexpression induced apoptosis, evidenced by morphological changes and altered expression of apoptosis-related proteins (increased Bax and p53, decreased Bcl2).
Conclusions:
- CSPG4P12 acts as a tumor suppressor in NSCLC.
- CSPG4P12 inhibits NSCLC development and tumorigenesis by activating the mitochondrial apoptotic pathway involving p53, Bcl2, and Bax.
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