The interruption of normal cell cycle execution acts as an important part to the development of leukemia. It was reported that microRNAs (miRNAs) were closely related to tumorigenesis and progression, and their aberrant expression had been demonstrated to play a crucial role in numerous types of cancer. Our previous study showed that miR-1246 was preferentially overexpressed in chemo-resistant leukemia cell lines, and participated in process of cell cycle progression and multidrug resistant regulation. However, the underlying mechanism remains unclear. In present study, bioinformatics prediction and dual luciferase reporter assay indicated that CADM1 was a direct target of miR-1246. Evidently decreased expression of CADM1 was observed in relapsed primary leukemia patients and chemo-resistant cell lines. Our results furtherly proved that inhibition of miR-1246 could significantly enhance drug sensitivity to Adriamycin (ADM), induce cell cycle arrest at G0/G1 phase, promote cell apoptosis, and relieve its suppression on CADM1 in K562/ADM and HL-60/RS cells. Interference with CADM1 could reduce the increased drug sensitivity induced by miR-1246 inhibition, and notably restore drug resistance by promoting cell cycle progression and cell survival via regulating CDKs/Cyclins complexes in chemo-resistant leukemia cells. Above all, our results demonstrated that CADM1 attenuated the role of miR-1246 in promoting cell cycle progression and cell survival, thus influencing multidrug resistance within chemo-resistant leukemia cells via CDKs/Cyclins. Higher expression of miR-1246 and lower expression of CADM1 might be risk factors for leukemia.

OBJECTIVE: To explore the relationship between CADM1 expression and sensitivity to TPF-induced chemotherapy in laryngeal squamous cell carcinoma (LSCC) patients, then investigate its potential mechanisms.
METHODS: Differential CADM1 expression was examined in chemotherapy-sensitive and chemotherapy-insensitive LSCC patient samples after TPF-induced chemotherapy using microarray analysis. Receiver operating characteristic (ROC) curve analysis and bioinformatics approaches were used to investigate the diagnostic value of CADM1. Small interfering RNAs (siRNAs) were used to knock down CADM1 expression in an LSCC cell line. Differential CADM1 expression was compared by qRT-PCR assays in 35 LSCC patients treated with chemotherapy, including 20 chemotherapy-sensitive and 15 chemotherapy-insensitive patients.
RESULTS: Public database and primary patient data both suggest that CADM1 mRNA is expressed at lower levels in chemotherapy-insensitive LSCC samples, suggesting its potential usefulness as a biomarker. Knockdown of CADM1 with siRNAs led to decreased sensitivity of LSCC cells to TPF chemotherapy.
CONCLUSIONS: Upregulation of CADM1 expression can alter the sensitivity of LSCC tumors to TPF induction chemotherapy. CADM1 is a possible molecular marker and therapeutic target for induction chemotherapy in LSCC patients.

[This corrects the article DOI: 10.3389/fonc.2019.00569.].

OBJECTIVE: Long non-coding RNAs (lncRNAs) have great potential as therapeutic targets in hepatocellular carcinoma (HCC). In this study, we aimed to uncover the function and molecular mechanism of long intergenic non-protein coding RNA 1006 (LINC01006) in HCC.
METHODS: Mice were injected with HCC cells in order to establish the HCC model. Quantitative reverse transcription polymerase chain reaction was used to determine the expression levels of LINC01006, cell adhesion molecule 1 (CADM1), and microRNA (miR)-194-5p in HCC tissues and cells. The cell proliferation, invasion, and migration abilities were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, transwell, and wound healing assays. The interrelation between LINC01006, miR-194-5p, and CADM1 was confirmed by a dual-luciferase reporter assay. Western blotting was employed to assess the relative protein expression level of CADM1.
RESULTS: LINC01006 and CADM1 displayed upregulation, but miR-194-5p exhibited downregulation in HCC cells and tissues. Short hairpin (sh)-LINC01006 and miR-194-5p mimics repressed the proliferative, migratory, and invasive capacities of HCC cells, and injection of sh-LINC01006 restrained the growth of HCC tumours in mice. LINC01006 served as a competing endogenous RNA of miR-194-5p and was inversely correlated with miR-194-5p. CADM1 was targeted by miR-194-5p, inversely correlated with miR-194-5p, and positively associated with LINC01006. Furthermore, transfection of pcDNA-CADM1 or the miR-194-5p inhibitor reversed the suppressive effects of sh-LINC01006 on the proliferation, invasion, and migration abilities of HCC cells.
CONCLUSIONS: Downregulation of LINC01006 repressed the development of HCC by sponging miR-194-5p to modulate the expression of CADM1, implying its potential as a therapeutic target for HCC.

The cell adhesion molecule CADM1, which participates in cell adhesion and signal transduction, has a regulatory effect on the development of tumors. CADM1 is often involved in malignant tumors of multiple organ systems, such as the respiratory and digestive systems. Upregulated CADM1 promotes tumor cell apoptosis and inhibits malignant proliferation. Along with cell cycle-related proteins, it participates in regulating signaling pathways, such as EMT, STAT3, and AKT, and plays an important role in inhibiting invasion and migration. Considering clinical characteristics, low CADM1 expression is associated with aggressive tumors and poor prognosis. In addition, some long non-coding RNAs (lncRNAs) or miRNAs directly or indirectly act on CADM1 to regulate tumor growth and motility. Interestingly, CADM1 function differs in adult T-cell leukemia/lymphoma (ATLL), and NF-κB is thought to be involved in this process. Taken together, CADM1 could be a potential biomarker for early diagnosis and a target for cancer treatment in future clinical practices.

Serum microRNA has been demonstrated as a noninvasive predictor for the progression of non-small-cell lung cancer (NSCLC). The role of microRNA-486-5p (miR-486-5p) in NSCLC seems to be paradoxical. On the one hand, elevated expression of miR-486-5p in serum is associated with unfavorable survival; on the other hand, miR-486-5p was notably reduced in NSCLC tissues and acted as a tumor-suppressor to inhibit NSCLC metastasis. The expression of miR-486-5p was analyzed in serum and tissue samples and their relationship was explored. The miR-486-5p-expressing cells were isolated by fluorescent-activated cell sorting. The downstream target of miR-486-5p was identified by bioinformatics prediction and experimental confirmation. Functional studies of miR-486-5p on NSCLC metastasis were determined by endothelial permeability assay and trans-endothelial invasion assay. We found that the expression of miR-486-5p was remarkably increased in serum, while dramatically downregulated in tumor tissues of NSCLC. However, the level of miR-486-5p in serum was positively correlated with that in tumor tissues. Next, we identified CD31+ vascular endothelial cells in the lung stroma as miR-486-5p-expressing cells. According to bioinformatics prediction, quantitative real-time reverse transcription PCR, luciferase reporter assay, and western blot, miR-486-5p directly targeted the cell adhesion molecule 1/tight junctions axis in vascular endothelial cells. In addition, endothelial permeability assay and trans-endothelial invasion assay confirmed that miR-486-5p promoted NSCLC metastasis. Highly elevated expression of miR-486-5p in CD31+ vascular endothelial cells increased vascular permeability and promoted NSCLC metastasis. In conclusion, stromal-derived miR-486-5p is responsible for the paradoxical effect of miR-486-5p in serum and tumor tissue.

At present, microRNAs and its downstream genes have been regarded as influential indicators in various malignancies. Therefore, the aim of this study was to explore the relationship and molecular mechanism of the miR-423-5p and its downstream gene CADM1 in the LUAD.
The pcDNA-CADM1 was used to construct the CADM1 overexpressed cell model. The cell proliferation was determined by CCK-8 and EdU assays and the cell metastasis was performed by wound scratch and transwell chamber assays. The relationship between miR-423-5p and CADM1 were determined by bioinformatics, luciferase reporter and western blot assays.
The results revealed that the CADM1 was downregulated in LUAD tissues and cell lines. CADM1 overexpression markedly repressed the cell proliferation, migration and invasion. Moreover, the results of bioinformatics, luciferase reporter and WB assays showed that CADM1 was a target gene of miR-423-5p and the miR-423-5p expression was negatively associated with CADM1 in LUAD cell lines. Finally, rescue experiments revealed that downregulation of CADM1 could antagonize the functions of miR-423-5p inhibitor on cell proliferation and metastasis. These results indicated that miR-423-5p aggravated lung adenocarcinoma via downregulation of CADM1 expression.
Downregulation of CADM1 could antagonize the functions of miR-423-5p inhibitor on cell proliferation and metastasis. miR-423-5p aggravated lung adenocarcinoma via downregulation of CADM1 expression.

Cell adhesion molecule 1 (CADM1) is frequently silenced in lung, prostate, liver, stomach, pancreatic and breast carcinomas and other forms of human carcinomas. However, it is unclear regarding the role of CADM1 in irritable bowel syndrome with diarrhoea (IBS-D) that is the most common gastrointestinal diagnosis and may contribute to impaired intestinal barrier function. The aim of the present study is to explore the potential mechanism of CADM1 in regulating intestinal barrier function in IBS-D. A rat model with IBS-D induced by the combination method of mother-infant separation, acetic acid and restraint stress was initially established. The defecation frequency, faecal water content (FWC), total intestinal permeability, sIgA, endotoxin, D-lactic acid and diamine oxidase (DAO) were then measured. Next, positive expression of CADM1 protein was detected in distal colonic tissue of rats by immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in distal colonic mucosa, CADM1, Janus kinase 1 (JAK1), STAT3, p-JAK1, p-STAT3, Claudin-1and Claudin-2 were evaluated using ELISA, RT-qPCR and western blot analysis. IBS-D rats exhibited low CADM1 expression and activated STAT3 signaling pathway. Overexpression of CADM1 in rats was shown to increase Claudin-1 expression, while decreasing expression of STAT3, Claudin-2, TNF-α and IL-6. In addition, silencing of CADM1 or inhibition of the STAT3 signaling pathway was demonstrated to improve the intestinal barrier function. Our study provides evidence that CADM1 can potentially improve intestinal barrier function in rats with IBS-D by inhibiting the STAT3 signaling pathway.

Aberrant expression of microRNAs may contribute to the initiation and progression of various types of human cancer and they may also constitute biomarkers for cancer diagnosis and treatment. However, the specific function of miR-194 in hepatocellular carcinoma (HCC), and the potential mechanism of its involvement in HCC were unclear. In the present study, we found that miR-194 inhibited CADM1 protein level expression by inhibiting mRNA translation of CADM1; the expression of CADM1 was low in liver cancer cells and tumor tissues, and the high expression of miR-194 was closely related to HCC. MiR-194 promoted proliferation, invasion, migration, and cell cycle progression of HCC cells, and such promotion effect was inhibited by CADM1. In addition, miR-194 may play a tumor-promoting action in a HCC xenograft tumor model. These results suggested that miR-194 may promote the occurrence and development of HCC by inhibiting CADM1. Therefore, miR-194 may be a promising novel therapy for diagnosis of hepatocellular carcinoma.

Background: Genes related to cell adhesion pathway have been implicated in the genetic architecture of attention-deficit/hyperactivity disorder (ADHD). Cell adhesion molecule 1, encoded by CADM1 gene, is a protein which facilitates cell adhesion, highly expressed in the human prefrontal lobe. This study aimed to evaluate the association of CADM1 genotype with ADHD, executive function, and regional brain functions. Methods: The genotype data of 10-tag single nucleotide polymorphisms of CADM1 for 1,040 children and adolescents with ADHD and 963 controls were used for case-control association analyses. Stroop color-word interference test, Rey-Osterrieth complex figure test, and trail making test were conducted to assess \"inhibition,\" \"working memory,\" and \"set-shifting,\" respectively. A subsample (35 ADHD versus 56 controls) participated in the nested imaging genetic study. Resting-state functional magnetic resonance images were acquired, and the mean amplitude of low-frequency fluctuations (mALFF) were captured. Results: Nominal significant genotypic effect of rs10891819 in \"ADHD-alone\" subgroup was detected (P = 0.008) with TT genotype as protective. The results did not survive multiple testing correction. No direct genetic effect was found for performance on executive function tasks. In the imaging genetic study for the \"ADHD-whole\" sample, rs10891819 genotype was significantly associated with altered mALFF in the right superior frontal gyrus (rSFG, peak t = 3.85, corrected P < 0.05). Specifically, the mALFFs in T-allele carriers were consistently higher than GG carriers in ADHD and control groups. Endophenotypic correlation analyses indicated a significant negative correlation between \"word interference time\" in Stroop (shorter \"word interference time\" indexing better inhibitory function) and mALFF in the rSFG (r = -0.29, P = 0.006). Finally, mediation analysis confirmed significant indirect effects from \"rs10891819 genotype (T-allele carriers)\" via \"mALFF (rSFG)\" to \"inhibition (\"word interference time\")\" (Sobelz = -2.47; B = -2.61, 95% confidence interval -0.48 to -4.72; P = 0.009). Conclusions: Our study offered preliminary evidence to implicate the roles of CADM1 in relation to prefrontal brain activities, inhibition function, and ADHD, indicating a potential \"gene-brain-behavior\" relationship of the CADM1 gene. Future studies with larger samples may specifically test these hypotheses generated by our exploratory findings.