RAB26 contributes to the progression of non-small cell lung cancer after being transcriptionally activated by SMAD3

Abstract

Non-small cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer, which constitutes the leading cause of cancer mortality. RAB26, a member of Rab GTPase superfamily, has been suggested to play a role in the tumorigenesis of NSCLC. The present work aimed to explore whether and how RAB26 contributed to the progression of NSCLC. NSCLC cell line A549 was transfection with short hairpin RNA (shRNA) or overexpression (Ov) vector to knockdown RAB26 or overexpress SMAD3, respectively. Then the malignant processes of A549 cells including proliferation, migration, invasion and apoptosis were evaluated by CCK-8, colony formation, wound-healing, transwell and TUNEL assays, respectively. Expression of proteins involved in these processes was measured by western blot. A549 xenograft mice model was established to confirm the effect of RAB26 silence on NSCLC progression in vivo. The relationship between RAB26 and SMAD3 was analyzed by bioinformatics and then verified by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. We found that silence of RAB26 inhibited the proliferation, migration and invasion but promoted apoptosis of A549 cells. In vivo studies revealed that the tumor growth of A549 xenograft was markedly suppressed upon RAB26 silence. Moreover, it was confirmed that SMAD3 bound to the promoter of RAB26 and enhance its expression. Finally, we observed that overexpression of SMAD3 significantly blocked the inhibitory effect of RAB26 silence on NSCLC progression. Collectively, RAB26 may contribute to the progression of NSCLC after being transcriptionally activated by SMAD3.

Targeting Rab26 to Conquer Cisplatin-Resistant Lung Cancer with Self-Assembled DNA Nanomaterials

“…32 Rab26 has been implicated in NSCLC progression in previous studies. 16,17 Importantly, our study showed that silencing Rab26 only slightly suppressed the proliferation of cisplatin-resistant A549/DDP lung cancer cells, but silencing Rab26 could partially reverse the cisplatin drug resistance of A549/DDP, suggesting that Rab26 is an essential regulator in the cisplatin resistance of A549/DDP. The regulation of cell autophagy (including mitophagy) can be an effective strategy to control resistance in lung cancer.…”

“…Rab26 has also been implicated in lysosome trafficking, mitochondrial redistribution, and autophagy induction in neuronal somata. , Rab26 is already known to be involved in lung cancer. Its expression gradually increased from stage I to VI in NSCLC tissues compared with normal tissues . Additionally, Rab26 supplementation partially restored oncogenicity, whereas it was inhibited in normal lung cancer cells .…”

“…Its expression gradually increased from stage I to VI in NSCLC tissues compared with normal tissues. 16 Additionally, Rab26 supplementation partially restored oncogenicity, whereas it was inhibited in normal lung cancer cells. 17 Some evidence suggests that targeted delivery of Rab26 siRNA could serve as lung cancer therapy for normal NSCLC, 18 but whether and how Rab26 contributes to drug resistance of NSCLC remain unclear.…”

Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis

“…The cell lysates were incubated with anti-SP1 (ab231778, 1:100, Abcam Inc., Cambridge, MA, USA) or normal rabbit antibody immunoglobulin G (IgG, ab172730, 1:100, Abcam) at 4°C overnight. The DNA was diluted using ChIP dilution buffer, and the abundance of SP1 was examined by qPCR [ 29 ].…”

Recent advances in conventional and unconventional vesicular secretion pathways in the tumor microenvironment

“…In line with this observation, a recent study showed that Rab3c promotes cell migration and correlates with poor prognosis in colon cancer by regulating the ability of cancer cells to release IL-6 via exocytosis and activating the JAK2-STAT3 pathway [56]. In addition, S-SMAD3, a key modulator in the TGF-β mediated transcriptional activation that drives epithelial-mesenchymal transition (EMT) and cell migration, binds to the promoter of Rab26 gene, thereby increasing its expression to enhance cancer progression [57]. This is suggestive of the Rab proteins' role in oncogenic signaling to direct tumor progression.…”