Upregulation of Linc00284 Promotes Lung Cancer Progression by Regulating the miR-205-3p/c-Met Axis

Abstract

Lung cancer (LC) is a malignant tumor with the highest incidence and mortality rates worldwide. Linc00284, a long non-coding RNA, is a newly discovered regulator of LC. This study aimed to explore the role of Linc00284 in LC progression. Gene expression levels were detected by RT-qPCR and/or western blot analysis. Cell migratory and invasive capabilities were measured by wound healing and transwell assays. Subcutaneous xenograft models were constructed to examine tumor growth of LC cells. Data showed that Linc00284 was significantly upregulated in LC tissues compared to adjacent normal lung tissues and predicted poor prognosis in patients with LC. In vitro, Linc00284 was highly expressed in LC cells and was mainly localized in the cytoplasm. Mechanistically, Linc00284 directly bound to miR-205-3p, leading to the upregulation of c-Met expression. A significant negative correlation was observed between Linc00284 and miR-205-3p expression levels, and the Linc00284 level was positively correlated with the c-Met expression. Linc00284/miR-205-3p/c-Met regulatory axis promotes LC cell proliferation, migration, and invasion. Furthermore, the in vivo results indicated that Linc00284 knockdown markedly suppressed tumor growth. Taken together, these data suggest that Linc00284 facilitates LC progression by targeting the miR-205-3p/c-Met axis, which may be a potential target for LC treatment.

Cytostatic Activity of Sanguinarine and a Cyanide Derivative in Human Erythroleukemia Cells Is Mediated by Suppression of c-MET/MAPK Signaling

“…This result was verified by assessment of the protein expression levels of p-MEK, p-ERK, p-mTOR, and p-STAT3, which are key targets in the downstream signaling pathway (Figure 6A,B). To further explore how c-MET protein expression levels were affected by 1 and 1a, we examined the mRNA expression levels of c-MET by RT q-PCR after compound treatment [37]. Intriguingly, c-MET mRNA levels in HEL cells were reduced in a dose-dependent manner with compound treatment, indicating that c-MET expression is subject to pretranscriptional regulation (Figure 6C); this indicates that c-MET and its downstream pathways are repressed, at least in part, through c-MET pretranscriptional regulation after treatment with 1 and 1a.…”

Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance

“…In addition to activating the PI3K/AKT signaling pathway, as mentioned above, lncRNA LINC01510 can activate the classical MAPK signaling pathway by upregulating MET to promote EGFR-TKI resistance ( Pal et al, 2022 ). Moreover, other lncRNAs, such as Linc00284, FAM83A-AS1, and LINC00857, were revealed to mediate lung cancer progression through the regulation of MET ( Su et al, 2020 ; Sheng et al, 2021 ; Zhao et al, 2022 ), but their roles in EGFR-TKI resistance need to be further explored.…”

Insights into the Mechanisms of Action of Proanthocyanidins and Anthocyanins in the Treatment of Nicotine-Induced Non-Small Cell Lung Cancer

“…Previous studies showed that microRNAs (miRs), including miR-205-3p, a class of noncoding RNA molecules, act as potential markers for the progression of NSCLC [ 102 , 103 ]. A recent in vitro experiment has suggested that the Aβ precursor protein-binding family B member 2 (APBB2)-mediated activation of dysregulated miR-205-3p expression in different NSCLC cells, including H460, H1299, 95-D, and A549, resulted in activation of proliferation and inhibition of apoptosis in NSCLC cells [ 104 ].…”

“…Taken together, nicotine-mediated activation of cell proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis in NSCLC cells can be modulated when PCs and ACNs interact with the active site of α7AChR, displaying complex modulation of several transcription/growth factors via signaling pathways involved in α7nAChR activation, suggesting that such compounds may have a significant role in the treatment of NSCLC (Figure 2). Previous studies showed that microRNAs (miRs), including miR-205-3p, a class of noncoding RNA molecules, act as potential markers for the progression of NSCLC [102,103]. A recent in vitro experiment has suggested that the Aβ precursor protein-binding family B member 2 (APBB2)-mediated activation of dysregulated miR-205-3p expression in different NSCLC cells, including H460, H1299, 95-D, and A549, resulted in activation of proliferation and inhibition of apoptosis in NSCLC cells [104].…”