LncRNA PART1 promotes lung squamous cell carcinoma progression via miR-185-5p/Six1 axis

Abstract

Dysregulation of the long non-coding RNA prostate androgen regulated transcript 1 (lncRNA PART1) is involved in the tumorigenesis of various cancers. However, little is known about its function and molecular mechanism in the development of lung squamous cell carcinoma (LSCC). In this study, we examined the expression of PART1 in LSCC clinical tissue samples and cell lines, and gain- and loss-of-function experiments were performed to explore the function of PART1 in LSCC proliferation, invasion and migration. We found that PART1 was overexpressed in both LSCC tissues and cell lines. Functional studies revealed that PART1 knockdown significantly suppressed cell proliferation, invasion and migration but enhanced apoptosis in LSCC cells, whereas overexpression of PART1 showed the opposite results. Mechanistically, we identified that PART1 acted as a sponge of miR-185-5p, and sineoculis homeobox homolog 1 (Six1) was a direct downstream target of miR-185-5p. Moreover, restoration of miR-185-5p or silencing of Six1 partially abolished the oncogenic effect of PART1 in LSCC cells. Clinically, The areas under the receiver operating characteristic (ROC) curve of PART1, miR-185-5p, and Six1 were 0.7857, 0.7332, 0.8112, respectively. Notably, high PART1, low miR-185-5p, and high Six1 expressions were significantly associated with severe clinical parameters and were the independent risk factors for poor prognosis of LSCC patients. Thus, we concluded that the PART1/miR-185-5p/Six1 axis might serve as a novel biomarker for the diagnosis and treatment of LSCC.

MiR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of non-small cell lung cancer cells

“…The investigators found that miR-185-5p attenuated the proliferative capacity of tumor cells, promoted tumor cell apoptosis, and delayed prostate cancer progression by downregulating RNCR3 expression [ 17 ]. Yu et al reported that miR-185-5p was under-expressed in lung squamous cell carcinoma tumor tissues and NSCLC cell lines, and low miR-185-5p expression was an independent risk factor for poor patient prognosis [ 18 ]. Additional studies reported that LncRNA MALAT1 and MDM4 were upregulated in NSCLC cells.…”

A review on the role of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) in the etiology of different disorders

“…Diagnostic value of PART1 has been evaluated in the context of esophageal squamous cell carcinoma ( Kang et al, 2018 ) and lung squamous cell carcinoma ( Cao et al, 2021 ) ( Table 6 ). In the former type of cancer, PART1 levels could differentiate between gefitinib responders and non-responders with AUC value of 0.839 ( Kang et al, 2018 ).…”

Activation of the Nrf2/GPX4 Signaling by Pratensein From Trifolium pretense Mitigates Ferroptosis in OGD/R-Insulted H9c2 Cardiomyocytes

“…In brief, cells were washed with cold PBS and resuspended in binding buffer and fixed, then incubated for 10 min in the dark with 5 μL Annexin V-FITC and 5 μL 7-AAD staining solution at room temperature. After mixing with 400 μL 1 × binding buffer, apoptosis was examined with FACS Calibur flow cytometer (Bection Dickinson) within 1 h. 18…”