Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

Abstract

Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirusdelivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells. Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

“…KIF21B is a potential oncogene that resists the induction of apoptosis and facilitates malignant tumorigenesis, tumor development, intrusion, and metastasis. Patients with high expression of KIF21B have been demonstrated to have a poorer prognosis in hepatocellular carcinoma (Zhao et al, 2020) and non-small cell lung cancer (Sun et al, 2020). SP6 is an important gene that regulates odontogenesis, belonging to a family of transcription factors that contain 3 classical zinc finger DNAbinding domains (Aurrekoetxea et al, 2016;Smith et al, 2020;Nakamura et al, 2020).…”

Association of human papillomavirus integration with better patient outcomes in oropharyngeal squamous cell carcinoma

“…HPV PCR-MassArray was performed as previously described. 31 In brief, this method detects and identifies 15 high-risk HPV subtypes (16,18,31,33,35,39,45,51,52,56,58,59, 66, 68, and 73), two low-risk subtypes (6 and 11), and HPV90, considered to be a possible highrisk subtype. The test included interrogation of human glyceraldehyde phosphate dehydrogenase (GAPDH) as a control for sample DNA quality and assay validity.…”

“…In this case, we were able to amplify a transcript that included KIF21B exon 2-KIF21B intron 2-HPV16 L1, indicating this integration resulted in alteration of splice sites such that intron 2 was retained in the transcript. KIF21B and other kinesin superfamily proteins have been implicated in the progression of many solid tumors via dysregulation of mitosis [44][45][46] ; therefore, it is of great interest to discover how this fusion may have played a role in the carcinogenesis in this case.…”

Identification of Novel Molecular Therapeutic Targets and Their Potential Prognostic Biomarkers Among Kinesin Superfamily of Proteins in Pancreatic Ductal Adenocarcinoma

“…In addition, KIF21A and KIF26A are responsible for microtubule stabilizers (12,13), while KIF2A and KIF19A are implicated in microtubule depolymerizers (14). In the past few years, numerous studies have indicated that kinesin's aberrant expression is involved in development and progress many kinds of cancers (15)(16)(17)(18)(19). As a member of KIFs, KIF18A can independently predict unfavorable prognosis in lung adenocarcinoma; overexpression of KIF18A can promote cell proliferation and inhibit apoptosis (20).…”