Particulate matter (PM10) destabilizes mitotic spindle through downregulation of SETD2 in A549 lung cancer cells

• Published in: Chemosphere (Oxford) Vol. 295; p. 133900
• Main Authors: Santibáñez-Andrade, Miguel, Sánchez-Pérez, Yesennia, Chirino, Yolanda I., Morales-Bárcenas, Rocío, Quintana-Belmares, Raúl, García-Cuellar, Claudia M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2022
• Subjects: A549; A549 Cells; Aneuploidy; Chromosomal instability; Down-Regulation; Humans; Lung Neoplasms - metabolism; Mitosis; Mitotic spindle; Particulate Matter - metabolism; Particulate Matter - toxicity; PM10; SETD2; Spindle Apparatus - genetics; Spindle Apparatus - metabolism; PM10; Aneuploidy; SETD2; Chromosomal instability; Mitotic spindle; A549; PM
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2022.133900

Air pollution represents an environmental problem, impacting negatively in human health. Particulate matter of 10 μm or less in diameter (PM10) is related to pulmonary diseases, including lung cancer. Mitotic spindle is made up by chromosome-microtubule (MT) interactions, where SETD2 plays an important role in MT stability. SETD2 binds and activates α-TUBULIN sub-unit and promotes MT polymerization. Alongside this mechanism, the spindle assembly checkpoint (SAC) senses the adequate mitotic progression through proteins such as BUBR1, AURORA B and SURVIVIN. Alterations in MT dynamics as well as in SAC cause aneuploidy and chromosomal instability, a common phenotype in cancer cells. In this study, we evaluated the effect of PM10 in the expression and protein levels of SETD2, as well as the effect in the expression and protein levels of SAC and mitotic components involved in chromosomal segregation/mitosis, using the A549 lung cancer cell line. A549 cell cultures were exposed to PM10 (10 μg/cm2) for 24 h to evaluate the expression and protein levels of SETD2 (SETD2), TUBA1A (α-TUBULIN), CCNB1 (CYCLIN B1), BUB1B (BUBR1), AURKB (AURORA B) and BIRC5 (SURVIVIN). We observed that PM10 decreases the expression and protein levels of SETD2, α-TUBULIN and BUBR1 and increases the levels of AURORA B and SURVIVIN in A549 cells, compared with non-treated cells. PM10 also caused a decrease in mitotic index and in the percentage of cells in G2/M when compared with control group. Co-localization of SETD2/α -TUB was lower in PM10-treated cells in comparison with non-treated cells. Finally, micronuclei (MN) frequency was higher in PM10-treated cells in contrast with non-treated cells, being whole chromosomes more common in PM10-treated MN than in non-treated MN. Our results suggest that PM10 causes missegregation and aneuploidy through downregulation of SETD2 and SAC components, inducing aneuploidy and predisposing to the generation of chromosomal instability in transformed cells. [Display omitted] •PM10 exposure reduces the expression and protein levels of SETD2 in A549 cells.•PM10 exposure alters the expression and protein levels of key mitotic regulators AURKB, BIRC5 and BUB1B.•PM10 reduces mitotic arrest and G2/M cell population in A549 cells via microtubule destabilization by SETD2.•PM10 exposure comprises SETD2/α-TUBULIN co-localization in the mitotic spindle.•Microtubule destabilization by PM10 exposure induces chromosomal instability in lung cancer cells.