Expression of lncRNA DLX6-AS1 in patients with hepatic carcinoma and its prognostic value.

Hepatic carcinoma (HCC) is one of the most common malignant tumors worldwide, and the prognosis of HCC patients is often poor. Long-chain non-coding RNA (lncRNA) distal-less homeobox 6 antisense 1 (DLX6-AS1) has been shown to be involved in the pathogenesis of various cancers. This study aims to investigate the expression of DLX6-AS1 in HCC patients and its prognostic value. The serum DLX6-AS1 was quantified using a reverse transcription-polymerase chain reaction (RT-PCR) assay in both HCC patients and healthy individuals, and the correlation of DLX6-AS1 with clinicopathological features of HCC patients, as well as the diagnostic and prognostic value of DLX6-AS1 for HCC patients, were analyzed. The results showed that the expression of serum DLX6-AS1 in HCC patients was significantly higher than that of healthy individuals (P < 0.05), and DLX6-AS1 was related to tumor differentiation, pathological staging, and lymph node metastasis (all P < 0.05). Patients with high DLX6-AS1 expression showed significantly higher mortality than those with low DLX6-AS1 expression, and the DLX6-AS1 expression in dead patients was significantly higher than that in living patients. Furthermore, the AUC of DLX6-AS1 for poor prognosis of HCC patients was larger than 0.8. The univariate analysis revealed that the poor prognosis of HCC patients was related to pathological staging, lymph node metastasis, differentiation, and DLX6-AS1 expression (all P < 0.05), and the Cox multivariate analysis revealed that pathological staging, lymph node metastasis, differentiation, and DLX6-AS1 expression were independent risk factors for poor prognosis of HCC patients (all P < 0.05). These findings suggest that DLX6-AS1 may be a promising target for diagnosis, treatment, and prognosis prediction of HCC patients.

Etomidate attenuates hyperoxia-induced acute lung injury in mice by modulating the Nrf2/HO-1 signaling pathway.

The present study aimed to investigate the protective effects of etomidate on hyperoxia-induced acute lung injury in mice, particularly on the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Fifty specific pathogen-free mice were randomly divided into the blank control, model, high oxygen exposure + low etomidate dose (0.3 mg·kg-1), a high oxygen exposure + moderate etomidate dose (3 mg·kg-1), and a high oxygen exposure + high etomidate dose (10 mg·kg-1) groups, with ten mice allotted per group. After 72 h, the mice were sacrificed and the lung tissues were harvested, and the wet-to-dry (W/D) ratio of the tissues was calculated. Hematoxylin-eosin staining was performed to observe the pathological changes in the lung tissues, and the lung injury score (LIS) was calculated. The mRNA and protein expression levels of Nrf2 and HO-1 were measured. The malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) levels were also measured, and interleukin (IL)-1ß, IL-6, tumor necrosis factor alpha (TNF-α) and IL-10 concentrations in the bronchoalveolar lavage fluid were determined. At low and moderate doses, etomidate decreased pathological damage in the lung tissue, decreased the LIS and W/D ratio, upregulated Nrf2 and HO-1 mRNA and protein expression, decreased IL-1ß, IL-6, and TNF-α concentrations, increased MPO activity and IL-10 levels, suppressed the production of the oxidation product MDA, and enhanced the activities of the antioxidant enzymes CAT and SOD. Within a certain dose range, etomidate enhanced antioxidant and anti-inflammatory effects in mice, thereby decreasing lung injury induced by the chronic inhalation of oxygen at high concentrations. Furthermore, the underlying mechanism may be associate with the upregulation of the Nrf2/HO-1 signaling pathway.

LncRNA-zinc finger protein 281 downregulates rho-associated coiled-coil containing protein kinase 1 by upregulating miR-144 in osteosarcoma.

Zinc finger protein 281 (ZNF281) has been characterized as a tumor suppressive lncRNA in glioma. The present study aimed to analyze the functionality of ZNF281 in osteosarcoma (OS). It was demonstrated that ZNF281 was downregulated in OS tissue specimens and predicted the survival of patients with OS. In tissues from patients with OS, ZNF281 was negatively associated with rho-associated coiled-coil containing protein kinase 1 (ROCK1), but positively associated with miR-144. In the U2OS cell line, ZNF281 overexpression mediated the upregulation of miR-44 and downregulation of ROCK1. miR-144 overexpression led to the downregulation of ROCK1, but failed to affect ZNF281. Expression of ZNF281 and miR-144 resulted in decreased cell migration and invasion, while ROCK1 overexpression resulted in increased invasion and migration of OS cells. In addition, ROCK1 overexpression attenuated the effects of ZNF281 and miR-144 overexpression. Thus, ZNF281 may downregulate ROCK1 by upregulating miR-144 and inhibit cancer cell invasion and migration in OS.

Effect of Long-Term Sodium Salicylate Administration on Learning, Memory, and Neurogenesis in the Rat Hippocampus.

Tinnitus is thought to be caused by damage to the auditory and nonauditory system due to exposure to loud noise, aging, or other etiologies. However, at present, the exact neurophysiological basis of chronic tinnitus remains unknown. To explore whether the function of the limbic system is disturbed in tinnitus, the hippocampus was selected, which plays a vital role in learning and memory. The hippocampal function was examined with a learning and memory procedure. For this purpose, sodium salicylate (NaSal) was used to create a rat animal model of tinnitus, evaluated with prepulse inhibition behavior (PPI). The acquisition and retrieval abilities of spatial memory were measured using the Morris water maze (MWM) in NaSal-treated and control animals, followed by observation of c-Fos and delta-FosB protein expression in the hippocampal field by immunohistochemistry. To further identify the neural substrate for memory change in tinnitus, neurogenesis in the subgranular zone of the dentate gyrus (DG) was compared between the NaSal group and the control group. The results showed that acquisition and retrieval of spatial memory were impaired by NaSal treatment. The expression of c-Fos and delta-FosB protein was also inhibited in NaSal-treated animals. Simultaneously, neurogenesis in the DG was also impaired in tinnitus animals. In general, our data suggest that the hippocampal system (limbic system) may play a key role in tinnitus pathology.

Toxic effects of arsenic trioxide on Echinococcus granulosus protoscoleces through ROS production, and Ca2+-ER stress-dependent apoptosis.

Cystic echinococcosis is a severe parasitic disease that commonly affects the liver and causes abscesses or rupture into the surrounding tissues, leading to multiple complications, such as shock, severe abdominal pain, and post-treatment abscess recurrence. Currently, there are no efficient measures to prevent these complications. We previously confirmed that arsenic trioxide (As2O3) exhibited in vitro cytotoxicity against Echinococcus granulosus protoscoleces. In the present study, we aimed to explore the mechanism of As2O3-induced E. granulosus protoscoleces apoptosis. After exposing E. granulosus protoscoleces to 0, 4, 6, and 8 µM As2O3, reactive oxygen species (ROS) level was detected by fluorescence microscopy; superoxide dismutase (SOD), and caspase-3 activities were measured; intracellular Ca2+ was detected by flow cytometry; GRP-78 and caspase-12 protein levels were measured by western blot analysis. Our results showed that the expression of caspase-3 was gradually increased and the expression of SOD was gradually decreased in As2O3-treated groups of protoscoleces. Simultaneously, fluorescence microscopy and flow cytometry showed that the ROS level and the intracellular Ca2+ level were increased in a time- and dose-dependent manner. Western blot analysis showed that the expressions of GRP-78 and caspase-12 were higher in As2O3-treated groups than in the control group. These results suggest that As2O3-induced apoptosis in E. granulosus protoscoleces is related to elevation of ROS level, disruption of intracellular Ca2+ homeostasis, and endoplasmic reticulum stress. These mechanisms can be targeted in the future by safer and more effective drugs to prevent recurrence of cystic echinococcosis.

Clinicopathological features of 11 Epstein-Barr virus-associated intrahepatic cholangiocarcinoma at a single center in China.

To date, only 20 cases of Epstein-Barr virus (EBV)-associated intrahepatic cholangiocarcinomas (IHCCs) have been reported in the literature.Pathology records of IHCC from January 1, 2007 to December 31, 2013 were retrieved from our hospital. Clinical information related to EBV-associated IHCC were also obtained, including gender, age at initial diagnosis, tumor size, tumor-node-metastasis stage, and follow-up duration. Surgically resected stage-matched EBV-negative IHCCs with full follow-up were selected for comparison. All liver specimens were fixed in 10% neutral-buffered formalin and paraffin-embedded tissue blocks containing cholangiocarcinoma and nonneoplastic liver tissue. Hematoxylin and eosin-stained sections were present in all cases.Among 329 primary IHCC patients, intranuclear expression of EBV was only found in 11 patients (3.3%), with an age range of 30 to 67 years (mean, 53.2 years; median, 54 years). The group consisted of 4 male and 7 female patients (M:F ratio 1:1.8). Histopathological analysis showed 1 case (9.1%) belonged to the typical lymphoepithelioma-like carcinoma (LELC), primarily composed of undifferentiated tumor cells intimately admixed with abundant lymphoplasmacytic cells. Two cases (18.2%) belonged to the conventional-type IHCCs, showing irregularly shaped neoplastic glands and scattered lymphoplasmacytic infiltration. The remaining 8 cases (72.7%) belonged to the lymphoepithelioma-like cholangiocarcinomas (LELCCs), showing varied glandular differentiation and dense lymphoplasmacytic infiltration. The overall survival of EBV-positive IHCCs was not significantly different from that of EBV-negative IHCCs (P = 0.512).Our data demonstrate that EBV-associated IHCC is very rare and may be subclassified into 3 different pathological types including LELC, conventional-type IHCC and LELCC on the basis of the tumor cellular differentiation, and host cellular immune responses in the tumors. The etiological, clinical, pathological, and molecular features are needed to be future studied by multicentric efforts in recruiting more EBV-associated IHCC patients.

Over-Expression of Cyclin D1 Promotes NSCs Proliferation and Induces the Differentiation into Astrocytes Via Jak-STAT3 Pathways.

Precise control of the proliferation and differentiation of multipotent neural stem cells (NSCs) is crucial for the proper development of the nervous system. Although cyclinD1 has been implicated as a cause of cancer in many studies, its roles in NSCs remain elusive. In this study, we examined the over-expression of cyclinD1 in controlling the self-renewal and differentiation of NSCs. Moreover, we found that the over-expression of cyclinD1 can drive cells to enter S phase and support the clonal self-renewing growth of NSCs. During the differentiation of NSCs, the over-expression of cyclinD1 promoted the generation of astrocytes, and their promotion likely occurred through synergistic phosphorylation of the signal transducer and activator of transcription 3. Our data suggest that the over-expression of cyclinD1 promotes the proliferation of NSCs and induces their differentiation into astrocytes via Jak-STAT3 pathways.

Serum carcinoembryonic antigen and carbohydrate antigen 19-9 for prediction of malignancy and invasiveness in intraductal papillary mucinous neoplasms of the pancreas: A meta-analysis.

The clinical importance of intraductal papillary mucinous neoplasms (IPMN) of the pancreas has been increasing due to the large number of newly diagnosed cases. A meta-analysis was used to assess the accuracy of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for the identification of malignant and invasive IPMN. A literature search of PubMed and Web of Knowledge was conducted. Studies included in the analysis addressed the diagnostic accuracy of serum CEA and CA19-9 and pooled estimates of sensitivity, specificity, positive- and negative-likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and receiver operating characteristic curves were calculated using random-effects models. Predefined subgroup analysis was performed. Fifteen studies (published between 2001 and 2013) were analyzed, including a total of 1,629 patients. Pooled estimates of CEA in malignant and invasive IPNM prediction were: Pooled sensitivity, 18 and 18%; pooled specificity, 93 and 95%; PLR, 2.83 and 3.54; NLR, 0.89 and 0.89; and DOR, 3.35 and 3.6, respectively. Pooled estimates of CA19-9 in malignant and invasive IPMN prediction were: Pooled sensitivity, 40 and 52%; pooled specificity, 89 and 88%; PLR, 2.93 and 3.78; NLR, 0.74 and 0.6; and DOR, 4.34 and 6.33, respectively. In conclusion, serum CEA has low sensitivity and high specificity for malignant and invasive IPMN. Serum CA19-9 is a useful non-invasive preoperative tool for differentiating between invasive and benign IPMN and should be taken into account in the decision to perform surgery.

Mitofusin-2 triggers mitochondria Ca2+ influx from the endoplasmic reticulum to induce apoptosis in hepatocellular carcinoma cells.

In previous studies, we confirmed that mitofusin-2 (Mfn2) induced apoptosis in hepatocellular carcinoma (HCC) cells. However, the exact molecular mechanism remained unclear. Mfn2 expressed lower in tumour tissues, compared with adjacent non-cancer tissues. Furthermore, Mfn2 immunostaining was very weak in HCC tissue (P < 0.05) and was significantly associated with tumour size and TNM stage (P = 0.038 and 0.040, respectively), and patients with HCC with lower Mfn2 expression had a poorer prognosis. Overexpression of Mfn2 induced HepG2 cells apoptosis, reduced the mitochondrial membrane potential (ΔΨm) and endoplasmic reticulum (ER) calcium ion (Ca(2+)) concentrations, and elevated intracellular reactive oxygen species (ROS) and mitochondrial Ca(2+) concentrations. However, when HepG2 cells overexpressing Mfn2 were treated with both heparin and RU360, there was no induction of apoptosis, decline in ΔΨm or ER Ca(2+), or increase in intracellular ROS or mitochondrial Ca(2+). We also found downregulation in the expression of mitochondrial calcium uptake1 and 2 (MICU1 and MICU2) in cells transfected with Adv-Mfn2. Thus, we confirmed that Mfn2 induced apoptosis in HCC cells by triggering influx of Ca(2+) into the mitochondria from the ER.

Overexpression of ß3 Chains of Laminin-332 is Associated With Clinicopathologic Features and Decreased Survival in Patients With Pancreatic Adenocarcinoma.

BACKGROUND: Laminin-332 (LM-332, formerly termed laminin-5) is a heterotrimeric glycoprotein that promotes cellular adhesion and migration. The heterotrimer consists of an α3, a ß3, and a γ2 chain. The aim of this investigation was to clarify the clinicopathologic significance of laminin-332ß3 (LNß3) chain expression and determine its influence on survival in pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction was used to validate and detect the expression of LNß3 mRNA in 37 pancreatic carcinoma tissue specimens and non-neoplastic pancreatic tissue samples. In addition, the protein expression of LNß3 was detected by immunohistochemistry methods in 96 pancreatic carcinoma specimens and 90 non-neoplastic pancreatic tissues. We analyzed the association between immunohistochemically detected LNß3 expression in pancreatic ductal adenocarcinoma and clinicopathologic characteristics. Survival curves were completed using the Kaplan-Meier method and compared using log-rank analysis. RESULTS: Quantitative real-time polymerase chain reaction indicated that the relative value of LNß3 mRNA was 1.427±1.554 and 1.423±1.439 by 2 in pancreatic carcinoma and non-neoplastic pancreatic tissues, respectively, values that were not statistically associated (P=0.991). Immunostaining for LNß3 was expressed in all patients with pancreatic ductal adenocarcinoma. LNß3 expression was related to differentiation (P=0.000) and advanced stage (P=0.034). Tumors with low expression of LNß3 had a survival advantage compared with tumors that had high expression of LNß3 (P=0.016). Multivariate analysis indicated that location is an independent predictor of overall survival, whereas other clinicopathologic characteristics such as tumor size, duodenal invasion, differentiation, extent of invasion, hepatic metastasis, and expression of LNß3 were not. CONCLUSION: Our results suggest that LNß3 expression may play a key role in the progression and prognosis of pancreatic ductal adenocarcinoma.

Antioxidant therapy for patients with chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND & AIMS: Chronic pancreatitis is a progressive, inflammatory disease of pancreas characterized by significant abdominal pain, malabsorption, and diabetes mellitus. Antioxidant therapy has been proposed as an effective treatment for painful chronic pancreatitis. We performed a meta-analysis of trials in which antioxidant therapy was compared with placebo in chronic pancreatitis. METHODS: We searched six databases to identify relevant trials. Results are expressed as risk ratio (RR) or standardized mean difference (SMD) with accompanying 95% confidence intervals (CI). The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. RESULTS: Eight studies including 573 patients met the inclusion criteria. A meta-analysis of these studies revealed that the intervention of antioxidants was associated with a significant increase in patients with pain relief (RR, 2.15; 95% CI, 1.72-2.69; P < 0.00001), and a significant decrease in patients' need for analgesics (RR, 0.56; 95% CI, 0.40-0.78; P = 0.0006). For pain score, antioxidants improved pain tolerance in chronic pancreatitis patients (SMD: -0.41; 95% CI: -0.83 to -0.10; P = 0.0005). Additionally, antioxidants may cause some adverse reactions (RR, 4.22; 95% CI: 2.17-8.20; P < 0.0001). CONCLUSIONS: Based on current evidence, oxidative stress may play an important role in the pathophysiology of chronic pancreatitis, and administration of antioxidants to patients with painful chronic pancreatitis is effective in relieving pain. Antioxidant supplements may be advocated as one medical therapy for chronic pancreatitis patients with low antioxidant capacity in their blood.

All-trans retinoic acid and arsenic trioxide induce apoptosis and modulate intracellular concentrations of calcium in hepatocellular carcinoma cells.

We investigated the effects of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), alone and in combination, on apoptosis and intracellular calcium concentration in hepatocellular carcinoma (HepG2) cells. We used HepG2 cells to test the effects of ATRA and ATO, individually and in combination, on cell proliferation, apoptosis, and intracellular-free calcium concentration. The results indicate that each drug decreased cell proliferation, increased apoptosis, and increased intracellular-free calcium in a time- and dose-dependent manner. We also calculated the coefficients of drug interaction for sub-threshold administration of both drugs in combination (1 µmol/L each). ATRA and ATO acted synergistically in inhibition of cell proliferation and additively in the promotion of apoptosis. All-trans retinoic acid and ATO interacted synergistically to reduce cell proliferation in HepG2 cells.

Expression of CCL2 and CCR2 in the hippocampus and the interventional roles of propofol in rat cerebral ischemia/reperfusion.

The aim of the present study was to determine the roles of the chemotactic factor, chemokine ligand 2 (CCL2), and its receptor, chemokine receptor type 2 (CCR2), in the hippocampus of rats with cerebral ischemia/reperfusion injury. In total, 24 Sprague-Dawley rats, weighting 250-300 g, were randomly divided into three groups (n=8): Sham-operated (C group), cerebral ischemia/reperfusion injury (I/R group) and propofol-intervention (P group) groups. The rats were sacrificed at 6 h after the ischemia/reperfusion surgery, and the brains were obtained to isolate the hippocampus. The mRNA expression levels of CCL2 and CCR2 in the hippocampus were analyzed by quantitative polymerase chain reaction, while the protein expression levels of CCL2 and CCR2 were determined by western blot analysis. The expression levels of CCL2 and CCR2 in the procerebrum were markedly elevated in the I/R and P groups at 6 h after the ischemia/reperfusion surgery when compared with the C group (P<0.05). In addition, the mRNA expression levels of CCL2 and CCR2 decreased significantly in the P group as compared with that in the I/R group (P<0.05). Therefore, CCL2 and CCR2 may be involved in the mechanisms underlying cerebral ischemia/reperfusion injury, and propofol may protect the brain through regulating the expression of CCL2 and CCR2.

A meta-analysis of randomized controlled trials of low-volume polyethylene glycol plus ascorbic acid versus standard-volume polyethylene glycol solution as bowel preparations for colonoscopy.

BACKGROUND: Standard-volume polyethylene glycol (PEG) gut lavage solutions are safe and effective, but they require the consumption of large volumes of fluid. A new lower-volume solution of PEG plus ascorbic acid has been used recently as a preparation for colonoscopy. AIM: A meta-analysis was performed to compare the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. STUDY: Electronic and manual searches were performed to identify randomized controlled trials (RCTs) that compared the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. After a methodological quality assessment and data extraction, the pooled estimates of bowel preparation efficacy during bowel cleansing, compliance with preparation, willingness to repeat the same preparation, and the side effects were calculated. We calculated pooled estimates of odds ratios (OR) by fixed- and/or random-effects models. We also assessed heterogeneity among studies and the publication bias. RESULTS: Eleven RCTs were identified for analysis. The pooled OR for preparation efficacy during bowel cleansing and for compliance with preparation for low-volume PEG plus ascorbic acid were 1.08 (95% CI = 0.98-1.28, P = 0.34) and 2.23 (95% CI = 1.67-2.98, P<0.00001), respectively, compared with those for standard-volume PEG. The side effects of vomiting and nausea for low-volume PEG plus ascorbic acid were reduced relative to standard-volume PEG. There was no significant publication bias, according to a funnel plot. CONCLUSIONS: Low-volume PEG plus ascorbic acid gut lavage achieved non-inferior efficacy for bowel cleansing, is more acceptable to patients, and has fewer side effects than standard-volume PEG as a bowel preparation method for colonoscopy.

The performance of enhanced liver fibrosis (ELF) test for the staging of liver fibrosis: a meta-analysis.

BACKGROUND: The enhanced liver fibrosis test (ELF) has been shown to accurately predict significant liver fibrosis in several liver diseases. AIMS: To perform a meta-analysis to assess the performance of the ELF test for the assessment of liver fibrosis. STUDY: Electronic and manual searches were performed to identify studies of the ELF test. After methodological quality assessment and data extraction, pooled estimates of the sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and summary receiver operating characteristics (sROC) were assessed systematically. The extent of heterogeneity and reasons for it were assessed. RESULTS: Nine studies were identified for analysis. The pooled sensitivity, specificity, positive LR, negative LR, and DOR values of ELF test, for assessment of significant liver fibrosis, were 83% (95% CI=0.80-0.86), 73% (95% CI=0.69-0.77), 4.00 (95% CI=2.50-6.39), 0.24 (95% CI=0.17-0.34), and 16.10 (95% CI=8.27-31.34), respectively; and, for evaluation of severe liver fibrosis, were 78% (95% CI=0.74-0.81), 76% (95% CI=0.73-0.78), 4.39 (95% CI=2.76-6.97), 0.27 (95% CI=0.16-0.46), and 16.01 (95% CI: 7.15-35.82), respectively; and, for estimation of cirrhosis, were 80% (95% CI=0.75-0.85), 71% (95% CI=0.68-0.74), 3.13 (95% CI=2.01-4.87), 0.29 (95% CI=0.19-0.44), and 14.09 (95% CI: 5.43-36.59), respectively. CONCLUSIONS: The ELF test shows good performance and considerable diagnostic value for the prediction of histological fibrosis stage.

let-7 enhances osteogenesis and bone formation while repressing adipogenesis of human stromal/mesenchymal stem cells by regulating HMGA2.

Bone and fat cells share a common progenitor, stromal/mesenchymal stem cells (MSCs), that can differentiate into osteoblasts or adipocytes. Osteogenesis and adipogenesis of MSCs maintain homeostasis under physiological conditions. The disruption of this homeostasis leads to bone-related metabolic diseases. For instance, reduction in bone formation, which is usually accompanied by an increase in bone marrow adipogenesis, occurs with aging, immobility, or osteoporosis. Thus, it is crucial to gain an understanding of how osteogenic and adipogenic lineages of MSCs are regulated. Here, we present evidence that let-7 is a positive regulator of bone development. Using gain- and loss-of-function approaches, we demonstrate that let-7 markedly promotes osteogenesis and suppresses adipogenesis of MSCs in vitro. Moreover, let-7 could promote ectopic bone formation of MSCs in vivo. Subsequent studies further demonstrated that let-7's effects are mediated through the repression of high-mobility group AT-hook 2 (HMGA2) expression. RNAi depletion of HMGA2 could also enhance osteogenesis and repress adipogenesis. Overall, we found a novel role of let-7/HMGA2 axis in regulating the balance of osteogenesis and adipogenesis of MSCs. Thus, let-7 can be used as a novel therapeutic target for disorders that are associated with bone loss and adipocyte accumulation.